电针对脑缺血再灌注大鼠bFGF、CD34表达及EPCs功能的影响
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摘要
脑卒中是全球范围内导致死亡的主要疾病,目前已经成为仅次于心脏病和癌症的第三大致死原因。而缺血性中风的发病率约占中风的87%,是脑卒中的主要类型,具有发病率高、致残率高、复发率高、死亡率高等特点,给患者及其家庭带来了痛苦,也对社会医疗体系造成了沉重的经济负担。
缺血性中风引起的脑缺血及继发的再灌注会导致严重的脑损伤。尽快恢复脑损伤后的血液供应,挽救濒临死亡的神经元、神经胶质细胞和血管内皮细胞,是减轻脑缺血后脑损伤的关键。如何诱导血管形成来促进缺血周边血管发生或侧支循环的建立,在已阻塞或狭窄的动脉周围组成内生的旁路循环,实现损伤组织缺血区的自我搭桥,是探求减轻缺血组织损伤、促进功能重建的应予关注之点。
我们在前期的一系列实验中发现,电针可以增加脑缺血再灌注损伤后大鼠骨髓和外周血中内皮祖细胞(Endothelial progenitor cells, EPCs)的数量,增强脑损伤区的血管内皮细胞生长因子(Vascular endothelial growth factor, VEGF)、血管内皮细胞生长因子受体2(Vascular endothelial growthFactor receptor2, VEGFR2)的表达。而EPCs与血管形成密切相关,同时能够参与内皮修复;VEGF则是EPCs动员、迁移、归巢过程中最有潜力的因子。这就说明针刺能够刺激机体产生相关的生长因子,并能够上调骨髓与外周血中EPCs的水平,与脑缺血再灌注损伤区的血管形成及内皮修复有关。此外,有研究报道碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)与VEGF在血管新生过程中起着协同作用,且能够促进内皮细胞的增殖、迁移,对神经元也有着积极影响；而CD34作为EPCs的一种表面抗原,也可以用来标记血管密度,以观察组织的血管生成情况。为了进一步研究针刺对脑缺血再灌注区域的EPCs表达及对血管修复情况的影响,我们拟观察针刺后不同时间点脑缺血再灌注损伤区的CD34+、bFGF的表达情况。
由于我们前期的实验都属于动物的在体实验,为了更清楚地观察针刺的效果,探索其相关机制,拟通过培养EPCs并采用“针灸血清”对其干预的方式进一步进行研究,以观察针刺对EPCs的增殖、迁移、黏附等能力的影响。
通过这一研究,我们将更进一步地探明针刺对脑缺血再灌注区域血管新生的影响及其对EPCs的作用,有可能使我们阐明针刺通过调理气血、疏通经络的作用促进损伤后血管发生的相关机理,对进一步探索针刺的治疗机理研究起到重要作用。
实验一电针对脑缺血再灌注大鼠bFGF、CD34表达的影响
目的：观察电针及预电针对脑缺血再灌注大鼠缺血大脑皮层bFGF和CD34表达的影响,探讨电针对脑缺血后血管形成的影响。
方法：雄性SD大鼠随机分为正常组、假手术组、模型组、电针组、预电针组,后三组制造大脑中动脉闭塞(Middle cerebral artery occlusion, MACO)模型。预电针组与电针组取“后三里”和“曲池”穴,分别于MACO造模前、后进行电针治疗。采用免疫组化法观察各组在MACO再灌注后12h、24h、48h三个时间点时缺血大脑皮层bFGF和CD34的表达情况。
结果：
(1)正常组及假手术组bFGF、CD34阳性表达较少。
(2)模型组bFGF阳性表达在脑缺血再灌注后12h处于较低水平,随时间延长呈现上升趋势,24h基本达到峰值,此后又逐渐下降；CD34则由脑缺血再灌注后12h的低值开始,随着时间的延长,呈上升趋势,至48h仍在上升；二者各时间点均与正常组及假手术组有明显差异。
(3)电针组bFGF阳性表达在脑缺血再灌注后12h时与模型组无明显差异,此后呈快速上升趋势且在24h、48h时均于模型组有明显差异：CD34阳性表达在12-24h时上升速度明显较模型组为快,而在24-48h时上升速度基本与模型组平行,在12h与模型比较无明显差异,24h、48h则明显较模型组为高,有明显差异；
(4)预电针组bFGF呈快速上升趋势且下降速度较缓,各时间点相较于模型组、电针组也均有明显差异;CD34阳性表达呈持续上升趋势,各时间点均与模型组、电针组有明显差异。
结论：电针及预电针都能明显提高脑缺血再灌注大鼠缺血大脑皮层bFGF和CD34的表达,能够为血管生成创造有利条件。
实验二内皮祖细胞的分离、培养与鉴定
目的：探讨Sprague Dawley (SD)大鼠骨髓源性EPCs分离、培养与鉴定的方法。
方法：通过密度梯度离心法从4周龄SD大鼠骨髓中分离单个核细胞,使用EGM-2MV培养基进行诱导培养,采用形态学特征观察、摄取Dil-Ac-LDL与结合FITC-UEA-1试验、免疫荧光化学鉴定其表面抗原CD133与VEGFR2等方法对其进行鉴定,并通过管腔形成实验观察形成管腔的能力。
结果：
(1)形态学观察：分离的BMNCs经诱导培养后,在生长的早(第8天左右)、晚期(第15天左右)其细胞形态有一定差异,早期以纺锤形、三角形、圆形细胞多见,晚期以圆形、短梭形细胞多见；
(2)摄取Dil-Ac-LDL与结合FITC-UEA-1实验：显示第8天、第21天的细胞均为阳性;
(3)免疫荧光化学染色：第8天的细胞表达CD133、VEGFR2;
(4)管腔形成实验：在Matrigel基质上15h左右能够生成血管样结构。
结论：利用密度梯度离心法分离大鼠BMNCs后以EGM-2MV进行诱导培养,可以获得两种不同形态的细胞；经过鉴定证明获得的细胞符合EPCs的特征；本方法能够简单、快速、可靠、大量地获取EPCS。
实验三针刺血清对内皮祖细胞增殖、迁移、黏附功能的影响
目的：探讨电针血清及预电针血清对体外培养的EPCs增殖、迁移、黏附等功能的影响。
方法：实验一中模型组、电针组、预电针组分别于再灌注48h时获取各组血清,同期获取正常组血清。将不同处理组的血清加至体外分离、培养、鉴定过的SD大鼠骨髓来源的EPCs,并设对照组,采用MTT法确定体外干预时合适的血清浓度,再分别采用MTT法、迁移实验、黏附实验观察各组血清对EPCs (?)曾殖、迁移、黏附能力的影响。
结果：
(1)20%浓度的预电针血清体外培养的EPCs(?)曾殖能力影响最显著；
(2)预电针组血清对体外培养的EPCs增殖、迁移、黏附能力影响最显著,与正常红、模型组、电针组比较有显著差异；
(3)电针血清可以提高体外培养的EPCs增殖、迁移、黏附能力,其迁移、黏附能力与模型组、正常组比较有显著差异；增殖能力与模型组无明显差异,与正常组比较有显著差异。
(4)模型组血清可以提高体外培养的EPCs增殖、迁移、黏附能力,与正常组比较有显著差异;
(5)正常组的EPCs增殖、迁移、黏附能力较对照组为高,与对照组相比有明显差
结论：电针血清及预电针血清均能明显提高EPCs的增殖、迁移、黏附能力,这可能是电针能促进缺血、损伤后组织修复和血管形成的因素之一,是针灸能够“行气血、通经络”原因之一。
Stroke is the major disease which leads to death in the worldwide. At present, it have become the third largest cause of death only less than heart disease and cancer. Among all strokes,87%is ischemic, which is the main type of stroke with high morbidity, disability, mortality, recurrence, and so on. Ischemic stroke harms to patients and their families seriously, also imposes a significant economic burden on our healthcare system.
Ischemic stroke brought about cerebral lack of blood, and the secondary reperfusion also can induce to severe brain damage. To return the blood supply of injuried brain as soon as possible and save the dying neurons, glial cells and vascular endothelial cells, which is the key to reduce injury of ischemic stroke. How to induce angiogenesis to promote the establishment of ischemic peripheral vascular or collateral circulation, is the most important for reducing tissue damage and promoting the functional reconstruction.
In a series of experiment, we found that electroacupuncture can increase endothelial progenitor cells (EPCs) of bone marrow and peripheral blood in rat after cerebral ischemia and reperfusion injury, also can enhance the expression of VEGF, VEGFR2in the brain. While EPCs has close correlation with angiogenesis, also can participate in endothelial repair; VEGF is the most potential factor for EPCs in the process of which mobilization, homing, migration. It showed that acupuncture can stimulate the body to produce growth factors which related to EPCs, and promote the angiogenesis and endothelial repair. In addition, other studies have reported that bFGF and VEGF play a synergistic role in the process of angiogenesis, which can promote endothelial cell proliferation, migration, also had a positive effect on neuron; CD34is a surface antigen of EPCs, also can be used to mark the microvascular density to observe the angiogenesis of tissue. In order to research further the effect of acupuncture on EPCs expression and repairment of blood vessels in the region of cerebral ischemia-reperfusion, we intend to observe the expression of CD34+, bFGF in different time points.
Our previous experiment belonged to the animal experiment. In order to observe the effects of acupuncture more clearly, and explore its mechanism, we intend to clture EPCs and use the "acupuncture serum" to intervene the EPCs for observing the effect of acupuncture on EPCs proliferation, migration, adhesion and so on. The "acupuncture serum" refers to the serum collected from the human or animal body which were treated by acupuncture or moxibustion.
Through this research, we will further study the effects of acupuncture on the angiogenesis and EPCs after the cerebral ischemia-reperfusion, which may enable us to clarify the mechanism of promoting angiogenesis after injury by means of acupuncture promoting the move qi and blood and dredging collateral channels, also can play an important role for further exploring the mechanism of acupuncture treatment.
PART ONE The effect of acupuncture on expression of bFGF, CD34in rats with cerebral ischemia reperfusion
Objective: To observe the effect of electroacupuncture on expression of bFGF and CD34in ischemic cerebral cortex of cerebral ischemia-reperfusion rat, to study the influence of electroacupuncture on promoting angiogenesis after cerebral ischemia.
Methods: male SD rats were randomly divided into normal group, sham-operated group, model group, electroacupuncture group and pre-electroacupuncturc group, later three groups manufactured middle cerebral artery occlusion (MACO) model. The pre-electroacupuncture group and electroacupuncture group cured separately before or after modeling using "Housanli(ST36)" and "Quchi(LT1L)" point. bFGF and CD34expression was observed in ischemic cerebral cortex of MACO rats after reperfusion12hours,24hours,48hours using immunohistochemistry.
Result.
(1) In normal group and sham operation group, the positive of CD34and bFGF was less.
(2) The positive bFGF in model group was at a low level after cerebral ischemia-reperfusion12hours, later it increased with change of Lime, after cerebral ischemia-reperfusion24hours, it reached the peak, then gradually decreased; CD34was at a low value after cerebral ischemia-reperfusion12hours, with the extension of time, the rise began, and it still rose after cerebral ischemia-reperfusion48hours. bFGF and CD34in model group were different obviously from the normal group and sham-operated group at each time point.
(3) The positive bFGF in the electroacupuncture group had no significant difference with the model group after cerebral ischemia-reperfusion12hours, then it rapidly increased and had significant difference with the model group after cerebral ischemia-reperfusion24and48hours; the positive CD34had a rapid rise after cerebral ischemia-reperfusion12~24hours, while after cerebral ischemia-reperfusion24~48hours, it rose in parallel to model group, after cerebral ischemia-reperfusion12hours, the positive CD34had no significant difference with the model group, but after24and48hours, it higher than in model group and had significant difference;
(4) the bFGF in pre-electroacupuncture group rose rapidly and descended slowly, which was different obviously with the model group and electroacupuncture group at each time point; the expression of CD34rose persistently and was different obviously with the model group and electroacupuncture group at each time point. Conclusion: Electroacupuncture and the pre-electroacupuncture can obviously increase the expression of bFGF and CD34in ischemic cerebral cortex of cerebral ischemia-reperfusion rat, contribute to angiogenesis.
PART TWO SD rat bone marrow-derived endothelial progenitor cells isolation, culture and characterization
Objective:To study the isolation, culture and identification of Sprague Dawley (SD)rat bone marrow-derived EPCs.
Methods:Bone marrow mononuclear cells (BMMNCs) were isolated"from bone, marrow of SD rats (4weeks old) by density gradient centri fugation, and cultured by EGM-2MV medium. Then identified the cell by observing the morphology, the assay of "ptaking Dil-Ac-LDL and combining with FITC-UEA-1,the expression of surface (?)igens CD133and VEGFR2by fluorescent immunocytochemistry, and evaluating the formation capillary ability through the tube formation assay on matrigel.
Results:
(l)Morphology:After culturing of the separated BMMNCs, the shape was different in the early (about8th day) and later (about10th day) of growth stage. In the early, they were spindle, triangle and round;In the later, they showed round and short spindle appearance
(2)The assay of uptaking Dil-Ac-LDL and combing with FITC-UEA-1:Both the8th and21th cells were all positive;
(3)Fluorescent immunocytochemistry:The8th cells expressed CD133and VFGFR2;
(4)Tube formation assay:FPCs formed capillary-like formations after about15hours when plated on matrigel.
Conclusion: We can isolate the rat BMMNCs using density gradient centri fugation and then culture them with EGM-2MV medium. The aquired colls were proved to be consistent with the characteristics of EPCs. This method is simple, quick, reliable to get enough EPCs.
PART THREE Effects of acupuncture serum on proliferation, migration, adhesion of rat bone marrow-derived EPCs
Objective: To study and investigate the effect of electroaeupuncture scrum and pre-electroacupuncture serum on the proliferation, migration, adhesion of cultured EPCs.
Methods: In experiment one, we got the serum after cerebral ischemia-reperfusion48hours from the model group,the electroacupuncture group and the pre-electroacupuncture group, meanwhile obtained the normal serum. Adding different serum to the cultured rat bone marrow-derived EPCs, and set the control group, using MTT method to determi ne the su itabl e concent ration of serum in vitro intervention, then using the MTT assay, migration assay, adhesion assay to observe the effect of electroacupuncture.
Results:
(1) In vitro, the most significant proliferal ion of EPCs was the concern rat ion of20%which came from pre-electroacupuncture
(2) Pre-electroacupuncture serum had the most sigrnficanl effect on EPCs proliferation, migration, adhesion, which was different significantly from the normal group, model group, and electroacupuncture group;
(3) Electroacupuncture serum can enhance the proliferation, migration, adhesion of EPCs in vitro. The migration and adhesion was di fferent significantly from the normal group and model group; The proliferation was different significantly from the normal group.
(4) Model group serum can enhance the proliferation, migration, adhesion of EPCs in vitro, which was significantly different with the normal group;
(5) In normal group, EPCs prol i ferat ion, migration, adhesi on abilit y was higher than the control group, also had obvious difference compared with control group.
Conclusion: ElecLroacupuncture and pro-electroacupuncturc serum can obviously enhance the proliferation, migration, adhesion of EPCs, this may be one of the factors that the Electroacupuncture therapy can promote tissue repair and neovascularization after injury and ischemia, also may be the effect of acupuncture can " move the Qi and blood, smooth t ho main and col lateral channels".
缺血性中风引起的脑缺血及继发的再灌注会导致严重的脑损伤。尽快恢复脑损伤后的血液供应,挽救濒临死亡的神经元、神经胶质细胞和血管内皮细胞,是减轻脑缺血后脑损伤的关键。如何诱导血管形成来促进缺血周边血管发生或侧支循环的建立,在已阻塞或狭窄的动脉周围组成内生的旁路循环,实现损伤组织缺血区的自我搭桥,是探求减轻缺血组织损伤、促进功能重建的应予关注之点。
我们在前期的一系列实验中发现,电针可以增加脑缺血再灌注损伤后大鼠骨髓和外周血中内皮祖细胞(Endothelial progenitor cells, EPCs)的数量,增强脑损伤区的血管内皮细胞生长因子(Vascular endothelial growth factor, VEGF)、血管内皮细胞生长因子受体2(Vascular endothelial growthFactor receptor2, VEGFR2)的表达。而EPCs与血管形成密切相关,同时能够参与内皮修复;VEGF则是EPCs动员、迁移、归巢过程中最有潜力的因子。这就说明针刺能够刺激机体产生相关的生长因子,并能够上调骨髓与外周血中EPCs的水平,与脑缺血再灌注损伤区的血管形成及内皮修复有关。此外,有研究报道碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)与VEGF在血管新生过程中起着协同作用,且能够促进内皮细胞的增殖、迁移,对神经元也有着积极影响；而CD34作为EPCs的一种表面抗原,也可以用来标记血管密度,以观察组织的血管生成情况。为了进一步研究针刺对脑缺血再灌注区域的EPCs表达及对血管修复情况的影响,我们拟观察针刺后不同时间点脑缺血再灌注损伤区的CD34+、bFGF的表达情况。
由于我们前期的实验都属于动物的在体实验,为了更清楚地观察针刺的效果,探索其相关机制,拟通过培养EPCs并采用“针灸血清”对其干预的方式进一步进行研究,以观察针刺对EPCs的增殖、迁移、黏附等能力的影响。
通过这一研究,我们将更进一步地探明针刺对脑缺血再灌注区域血管新生的影响及其对EPCs的作用,有可能使我们阐明针刺通过调理气血、疏通经络的作用促进损伤后血管发生的相关机理,对进一步探索针刺的治疗机理研究起到重要作用。
实验一电针对脑缺血再灌注大鼠bFGF、CD34表达的影响
目的：观察电针及预电针对脑缺血再灌注大鼠缺血大脑皮层bFGF和CD34表达的影响,探讨电针对脑缺血后血管形成的影响。
方法：雄性SD大鼠随机分为正常组、假手术组、模型组、电针组、预电针组,后三组制造大脑中动脉闭塞(Middle cerebral artery occlusion, MACO)模型。预电针组与电针组取“后三里”和“曲池”穴,分别于MACO造模前、后进行电针治疗。采用免疫组化法观察各组在MACO再灌注后12h、24h、48h三个时间点时缺血大脑皮层bFGF和CD34的表达情况。
结果：
(1)正常组及假手术组bFGF、CD34阳性表达较少。
(2)模型组bFGF阳性表达在脑缺血再灌注后12h处于较低水平,随时间延长呈现上升趋势,24h基本达到峰值,此后又逐渐下降；CD34则由脑缺血再灌注后12h的低值开始,随着时间的延长,呈上升趋势,至48h仍在上升；二者各时间点均与正常组及假手术组有明显差异。
(3)电针组bFGF阳性表达在脑缺血再灌注后12h时与模型组无明显差异,此后呈快速上升趋势且在24h、48h时均于模型组有明显差异：CD34阳性表达在12-24h时上升速度明显较模型组为快,而在24-48h时上升速度基本与模型组平行,在12h与模型比较无明显差异,24h、48h则明显较模型组为高,有明显差异；
(4)预电针组bFGF呈快速上升趋势且下降速度较缓,各时间点相较于模型组、电针组也均有明显差异;CD34阳性表达呈持续上升趋势,各时间点均与模型组、电针组有明显差异。
结论：电针及预电针都能明显提高脑缺血再灌注大鼠缺血大脑皮层bFGF和CD34的表达,能够为血管生成创造有利条件。
实验二内皮祖细胞的分离、培养与鉴定
目的：探讨Sprague Dawley (SD)大鼠骨髓源性EPCs分离、培养与鉴定的方法。
方法：通过密度梯度离心法从4周龄SD大鼠骨髓中分离单个核细胞,使用EGM-2MV培养基进行诱导培养,采用形态学特征观察、摄取Dil-Ac-LDL与结合FITC-UEA-1试验、免疫荧光化学鉴定其表面抗原CD133与VEGFR2等方法对其进行鉴定,并通过管腔形成实验观察形成管腔的能力。
结果：
(1)形态学观察：分离的BMNCs经诱导培养后,在生长的早(第8天左右)、晚期(第15天左右)其细胞形态有一定差异,早期以纺锤形、三角形、圆形细胞多见,晚期以圆形、短梭形细胞多见；
(2)摄取Dil-Ac-LDL与结合FITC-UEA-1实验：显示第8天、第21天的细胞均为阳性;
(3)免疫荧光化学染色：第8天的细胞表达CD133、VEGFR2;
(4)管腔形成实验：在Matrigel基质上15h左右能够生成血管样结构。
结论：利用密度梯度离心法分离大鼠BMNCs后以EGM-2MV进行诱导培养,可以获得两种不同形态的细胞；经过鉴定证明获得的细胞符合EPCs的特征；本方法能够简单、快速、可靠、大量地获取EPCS。
实验三针刺血清对内皮祖细胞增殖、迁移、黏附功能的影响
目的：探讨电针血清及预电针血清对体外培养的EPCs增殖、迁移、黏附等功能的影响。
方法：实验一中模型组、电针组、预电针组分别于再灌注48h时获取各组血清,同期获取正常组血清。将不同处理组的血清加至体外分离、培养、鉴定过的SD大鼠骨髓来源的EPCs,并设对照组,采用MTT法确定体外干预时合适的血清浓度,再分别采用MTT法、迁移实验、黏附实验观察各组血清对EPCs (?)曾殖、迁移、黏附能力的影响。
结果：
(1)20%浓度的预电针血清体外培养的EPCs(?)曾殖能力影响最显著；
(2)预电针组血清对体外培养的EPCs增殖、迁移、黏附能力影响最显著,与正常红、模型组、电针组比较有显著差异；
(3)电针血清可以提高体外培养的EPCs增殖、迁移、黏附能力,其迁移、黏附能力与模型组、正常组比较有显著差异；增殖能力与模型组无明显差异,与正常组比较有显著差异。
(4)模型组血清可以提高体外培养的EPCs增殖、迁移、黏附能力,与正常组比较有显著差异;
(5)正常组的EPCs增殖、迁移、黏附能力较对照组为高,与对照组相比有明显差
结论：电针血清及预电针血清均能明显提高EPCs的增殖、迁移、黏附能力,这可能是电针能促进缺血、损伤后组织修复和血管形成的因素之一,是针灸能够“行气血、通经络”原因之一。
Stroke is the major disease which leads to death in the worldwide. At present, it have become the third largest cause of death only less than heart disease and cancer. Among all strokes,87%is ischemic, which is the main type of stroke with high morbidity, disability, mortality, recurrence, and so on. Ischemic stroke harms to patients and their families seriously, also imposes a significant economic burden on our healthcare system.
Ischemic stroke brought about cerebral lack of blood, and the secondary reperfusion also can induce to severe brain damage. To return the blood supply of injuried brain as soon as possible and save the dying neurons, glial cells and vascular endothelial cells, which is the key to reduce injury of ischemic stroke. How to induce angiogenesis to promote the establishment of ischemic peripheral vascular or collateral circulation, is the most important for reducing tissue damage and promoting the functional reconstruction.
In a series of experiment, we found that electroacupuncture can increase endothelial progenitor cells (EPCs) of bone marrow and peripheral blood in rat after cerebral ischemia and reperfusion injury, also can enhance the expression of VEGF, VEGFR2in the brain. While EPCs has close correlation with angiogenesis, also can participate in endothelial repair; VEGF is the most potential factor for EPCs in the process of which mobilization, homing, migration. It showed that acupuncture can stimulate the body to produce growth factors which related to EPCs, and promote the angiogenesis and endothelial repair. In addition, other studies have reported that bFGF and VEGF play a synergistic role in the process of angiogenesis, which can promote endothelial cell proliferation, migration, also had a positive effect on neuron; CD34is a surface antigen of EPCs, also can be used to mark the microvascular density to observe the angiogenesis of tissue. In order to research further the effect of acupuncture on EPCs expression and repairment of blood vessels in the region of cerebral ischemia-reperfusion, we intend to observe the expression of CD34+, bFGF in different time points.
Our previous experiment belonged to the animal experiment. In order to observe the effects of acupuncture more clearly, and explore its mechanism, we intend to clture EPCs and use the "acupuncture serum" to intervene the EPCs for observing the effect of acupuncture on EPCs proliferation, migration, adhesion and so on. The "acupuncture serum" refers to the serum collected from the human or animal body which were treated by acupuncture or moxibustion.
Through this research, we will further study the effects of acupuncture on the angiogenesis and EPCs after the cerebral ischemia-reperfusion, which may enable us to clarify the mechanism of promoting angiogenesis after injury by means of acupuncture promoting the move qi and blood and dredging collateral channels, also can play an important role for further exploring the mechanism of acupuncture treatment.
PART ONE The effect of acupuncture on expression of bFGF, CD34in rats with cerebral ischemia reperfusion
Objective: To observe the effect of electroacupuncture on expression of bFGF and CD34in ischemic cerebral cortex of cerebral ischemia-reperfusion rat, to study the influence of electroacupuncture on promoting angiogenesis after cerebral ischemia.
Methods: male SD rats were randomly divided into normal group, sham-operated group, model group, electroacupuncture group and pre-electroacupuncturc group, later three groups manufactured middle cerebral artery occlusion (MACO) model. The pre-electroacupuncture group and electroacupuncture group cured separately before or after modeling using "Housanli(ST36)" and "Quchi(LT1L)" point. bFGF and CD34expression was observed in ischemic cerebral cortex of MACO rats after reperfusion12hours,24hours,48hours using immunohistochemistry.
Result.
(1) In normal group and sham operation group, the positive of CD34and bFGF was less.
(2) The positive bFGF in model group was at a low level after cerebral ischemia-reperfusion12hours, later it increased with change of Lime, after cerebral ischemia-reperfusion24hours, it reached the peak, then gradually decreased; CD34was at a low value after cerebral ischemia-reperfusion12hours, with the extension of time, the rise began, and it still rose after cerebral ischemia-reperfusion48hours. bFGF and CD34in model group were different obviously from the normal group and sham-operated group at each time point.
(3) The positive bFGF in the electroacupuncture group had no significant difference with the model group after cerebral ischemia-reperfusion12hours, then it rapidly increased and had significant difference with the model group after cerebral ischemia-reperfusion24and48hours; the positive CD34had a rapid rise after cerebral ischemia-reperfusion12~24hours, while after cerebral ischemia-reperfusion24~48hours, it rose in parallel to model group, after cerebral ischemia-reperfusion12hours, the positive CD34had no significant difference with the model group, but after24and48hours, it higher than in model group and had significant difference;
(4) the bFGF in pre-electroacupuncture group rose rapidly and descended slowly, which was different obviously with the model group and electroacupuncture group at each time point; the expression of CD34rose persistently and was different obviously with the model group and electroacupuncture group at each time point. Conclusion: Electroacupuncture and the pre-electroacupuncture can obviously increase the expression of bFGF and CD34in ischemic cerebral cortex of cerebral ischemia-reperfusion rat, contribute to angiogenesis.
PART TWO SD rat bone marrow-derived endothelial progenitor cells isolation, culture and characterization
Objective:To study the isolation, culture and identification of Sprague Dawley (SD)rat bone marrow-derived EPCs.
Methods:Bone marrow mononuclear cells (BMMNCs) were isolated"from bone, marrow of SD rats (4weeks old) by density gradient centri fugation, and cultured by EGM-2MV medium. Then identified the cell by observing the morphology, the assay of "ptaking Dil-Ac-LDL and combining with FITC-UEA-1,the expression of surface (?)igens CD133and VEGFR2by fluorescent immunocytochemistry, and evaluating the formation capillary ability through the tube formation assay on matrigel.
Results:
(l)Morphology:After culturing of the separated BMMNCs, the shape was different in the early (about8th day) and later (about10th day) of growth stage. In the early, they were spindle, triangle and round;In the later, they showed round and short spindle appearance
(2)The assay of uptaking Dil-Ac-LDL and combing with FITC-UEA-1:Both the8th and21th cells were all positive;
(3)Fluorescent immunocytochemistry:The8th cells expressed CD133and VFGFR2;
(4)Tube formation assay:FPCs formed capillary-like formations after about15hours when plated on matrigel.
Conclusion: We can isolate the rat BMMNCs using density gradient centri fugation and then culture them with EGM-2MV medium. The aquired colls were proved to be consistent with the characteristics of EPCs. This method is simple, quick, reliable to get enough EPCs.
PART THREE Effects of acupuncture serum on proliferation, migration, adhesion of rat bone marrow-derived EPCs
Objective: To study and investigate the effect of electroaeupuncture scrum and pre-electroacupuncture serum on the proliferation, migration, adhesion of cultured EPCs.
Methods: In experiment one, we got the serum after cerebral ischemia-reperfusion48hours from the model group,the electroacupuncture group and the pre-electroacupuncture group, meanwhile obtained the normal serum. Adding different serum to the cultured rat bone marrow-derived EPCs, and set the control group, using MTT method to determi ne the su itabl e concent ration of serum in vitro intervention, then using the MTT assay, migration assay, adhesion assay to observe the effect of electroacupuncture.
Results:
(1) In vitro, the most significant proliferal ion of EPCs was the concern rat ion of20%which came from pre-electroacupuncture
(2) Pre-electroacupuncture serum had the most sigrnficanl effect on EPCs proliferation, migration, adhesion, which was different significantly from the normal group, model group, and electroacupuncture group;
(3) Electroacupuncture serum can enhance the proliferation, migration, adhesion of EPCs in vitro. The migration and adhesion was di fferent significantly from the normal group and model group; The proliferation was different significantly from the normal group.
(4) Model group serum can enhance the proliferation, migration, adhesion of EPCs in vitro, which was significantly different with the normal group;
(5) In normal group, EPCs prol i ferat ion, migration, adhesi on abilit y was higher than the control group, also had obvious difference compared with control group.
Conclusion: ElecLroacupuncture and pro-electroacupuncturc serum can obviously enhance the proliferation, migration, adhesion of EPCs, this may be one of the factors that the Electroacupuncture therapy can promote tissue repair and neovascularization after injury and ischemia, also may be the effect of acupuncture can " move the Qi and blood, smooth t ho main and col lateral channels".
引文
[1]Yuan J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis,2009,14(4):469-477.
[2]Baron JC. Perfusion thresholds in human cerebral ischemia:historical perspective and therapeutic implications. Cerebrovasc Dis,2001, 11(suppl 1): 2-8.
[3]Kalogeris T, Baines CP, Krenz M, et al. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol,2012,298:229-317.
[4]Hermann DM, Zechariah A. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. J Cereb Blood Flow Metab,2009, 29(10):1620-1643.
[5]Chopp M, Li Y, Zhang J. Plasticity and remodeling of brain. J Neurol Sci, 2008,265(1-2):97-101.
[6]Han HS, Suk K. The function and integrity of the neurovascular unit rests upon the integration of thevascular and inflammatory cell systems. Curr Neurovasc Res,2005,2(5):409-423.
[7]Park JA, Choi KS, Kim SY, et al. Coordinated interaction of the vascular and nervous systems:fro mmolecule to cell-based approaches. Biochem Biophys Res Commun,2003,311 (2):247-253.
[8]Carmeliet P. Blood vessels and nerves:common signals, pathways and diseases. Nat Rev Genet,2003,4(9):710-720.
[9]Lok J, Gupta P, Guo S, et al. Cell-cell signaling in the neurovascular unit. Neurochem Res,2007,32(12):2032-2045.
[10]Hennigan A, O'Callaghan RM, Kelly AM. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans, 2007,35(Pt2):424-427.
[11]Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev,2005,57(2):173-185.
[12]del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab,2003,23(8):879-894.
[13]Chopp M, Li Y, Zhang J. Plasticity and remodeling of brain. J Neurol Sci, 2008,265(1-2):97-101.
[14]Ergul A, Alhusban A, Fagan SC. Angiogenesis:a harmonized target for recovery after stroke. Stroke,2012,43(8):2270-1174.
[15]Xiong Y, Mahmood A, Chopp M. Angiogenesis, neurogenesi s and brain recovery of function following injury. Curr Opin Investig Drugs,2010,11(3):298-308.
[16]Navaratna D, Guo S, Arai K, et al. Mechanisms and targets forangiogenic therapy after stroke. Cell Adh Migr,2009,3(2):216-223.
[17]Szpak GM, Lechowicz W, Lewandowska E, et al. Border zone neovascularization in cerebral ischemic infarct. Folia Neuropathol,1999,37(4):264-268.
[18]Hayashi T, Noshita N, Sugawara T, et al. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab,2003,23(2):166-180.
[19]Krupinski J, Issa R, Bujny T, et al. Aputative role for platelet-derived growth factor in angiogenesis and neuro protection after ischemic stroke in humans. Stroke,1997,28(3):564-573.
[20]Liu XS, Zhang ZG, Zhang RL, et al. Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells. J Cereb Blood Flow Metab,2007,27(3):564-574.
[21]Chen J, Cui X, Zacharek A, et al. Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke. J Cell Mol Mod,2009,13(7):1348-1357.
[22]Jiang WL, Zhang SP, Zhu HB, et al. Effect of 8-0-acetyl shanzhiside methylester increases angiogenesis and improves functional recoveryafter stroke. Basic Clin Pharmacol Toxicol,2011,108(1):21-27.
[23]Manoonkitiwongsa PS, Jackson-Friedman C, McMillan PJ, et al. Angiogenesis after stroke is correlated with increased numbers of macrophages:the clean-up hypothesis. J Cereb Blood Flow Metab,2001,21(10):1223-1231.
[24]Petraglia AL, Marky AH, Walker C, et al. Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact. Neurosurgery,2010,66(1):165-171; discussion 171-172.
[25]Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vasceular disorders. Blood,1998,91(10):3527-3561.
[26]Li N, Hu H, Lindqvist M, et al. Platelet-leukocyte cross talk in whole blood. Arterioscler Thromb Vasc Biol,2000,20(12):2702-2708.
[27]Esposito K, Marfella R, Ciotola M, et al. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome:a randomized trial. JAMA,2004,292(12):1440-1446.
[28]Baker RI, Eikelboom J, Lofthouse E, et al. Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood, 2001,98(1):36-40.
[29]Cherian P, Hankey GJ, Eikelboom JW, et al. Endothelial and platelet activation inacute ischemic stroke and its etiological subtypes. Stroke,2003, 34(9):2132-2137.
[30]Licata G, Tuttolomondo A, Di Raimondo D, et al. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost,2009,101(5):929-937.
[31]Hanson E, Jood K, Karlsson S, et al. Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke. J Thromb Haemost,2011, 9(2):275-281.
[32]畅慧君,张其相,卢红,等.急性脑梗死患者血清vWF的动态测定及临床研究.中国实用神经疾病杂志,2009,12(9)：1-3.
[33]Bongers TN, de Maat MP, van Goor ML, et al. High von Willebrand factor levels increase the risk of first ischemic stroke:influence of ADAMTS13, inflammation, and genetic variability. Stroke,2006,37(11):2672-2677.
[34]刘江,翟明,张蕾,等.昆明地区汉族人vWF基因多态性与急性脑梗死的相关性.中国神经精神疾病杂志,2011,37(9)：535-539.
[35]Carter AM, Catto AJ, Mansfield MW, et al. Predictive variables for mortality after acute ischemic stroke. Stroke,2007,38(6):1873-1880.
[36]Hanson E, Jood K, Nilsson S, et al. Association between genetic variation at the ADAMTS13 locus and ischemic stroke. J Thromb Haemost,2009, 7(12):2147-2148.
[37]Kleinschnitz C, De Meyer SF, Schwarz T, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood,2009,113(15):3600-3603.
[38]Deng AJ, Jing DY. Sequential changes of HIF-1 a protein and mRNA in hypoxic bovine retinal microvessels endothelial cells. Int J Ophthalmol,2005, 5(2):225-228.
[39]Bergeron M, Yu AY, Solway KE, et al. Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eu J Neurosci, 1999, 11(12) :4159-4170.
[40]Demougeot C, Van Hoecke M, Bertrand N, et al. Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2' -dipyridyl in the rat photothrombotic ischemic stroke model. J Pharmacol Exp Ther, 2004, 311 (3): 1080-1087.
[41]Demougeot C,Van Hoecke M,Bertrand N, et al. Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2'-dipyridyl in the rat photothromboticischemicstroke model.JPharmacolExp Ther,2004, 311(3) :1080-1087.
[42]Mattson MP, Camandola S. NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest, 2001, 107(3):247-254.
[43]Aggarwal BB, Takada Y, Shishodia S, el al. Nuclear transcription factor NF-kappaB: role i n biology and medicine. Indian J Exp Biol, 2004, 42(4) :34 1-353.
[44]Schneider A, Martin-Vi1lalba A, WeihF, etal. NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat. Mod, 1999, 5(5) : 554-559.
[45]Ridder DA, Schwaninger M. NF-kappaB signaling in cerebral ischemia. Neuroscience, 2009, 158(3):995-1006.
[46]Brines M, Cerami A. Discovering crythropoictin's extra-hematopoietic functions: biology and clinical promise. Kidney Int, 2006, 70(2):246-250.
[47]Hicklin DJ, Ellis LM. Role of the vascular endothel ialgrowt h factor pathway in tumor growth and angiogenesis. J Clin Oncol, 2005, 23(5):1011-1027.
[48]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-inducedvascular endothelial growth factor expression precedes ncovascularization after cerebral ischemia. Am J Pathol, 2000, 156(3):965 - 976.
[49]Hickl in DJ, Ell is LM. Role of the vascular endothel ialgrowlh factor pathway in tumor growth and angiogenesis. J Clin Oncol, 2005, 23(5):1011-1027.
[50]Li Q, Stephenson D. Post ischemic administration of basic fibroblast growth factor improves sensorimotor function andreduces in Caret size following permanent focal cerebral ischemiain the rat. Exp Neurol, 2002, 177 (2):531-537.
[51]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-induccdvascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol,2000,156(3):965-976.
[52]王韧,侯立军.VEGF和内皮抑素对血管生成作用的研究进展.重庆医学,2011,40(25)：2582-2585.
[53]Presta M, Dell'Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev,2005,16(2):159-178.
[54]Wiedlocha A, S(?)rensen V. Signaling, internalization, and intracellular activity of fibroblast growth factor. Curr Top Microbiol Immunol,2004, 286:45-79.
[55]Edwards AK, van den Heuvel MJ, Wessels JM, et al. Expression of angiogenic basic fibroblast growth factor, platelet derived growth factor, thrombospondin-1 and their receptors at the porcine maternal-fetal interface. Reprod Biol Endocrinol,2011,9:5.
[56]Li WL, Yamada Y, Ueno M, et al. Platelet-derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis. J Biochem,2006,140(2):267-273.
[57]Facchiano A, De Marchis F, Turchetti E, et al. The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor. J Cell Sci,2000,113(Pt 16):2855-2863.
[58]De Marchis F, Ribatti D, Giampietri C, et al. Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor. Blood,2002,99(6):2045-2053.
[59]Tengood JE, Ridenour R, Brodsky R, et al. Sequential delivery of basic fibroblast growth factor and platelet-derived growth factor for angiogenesis. TissueEng Part A,2011,17(9-10):1181-1189.
[60]高娜,吴涛.TGF-β在卵巢癌中作用的研究进展.大连医科大学学报,2012,34(4)：409-412.
[61]Bertolino P, Deckers M, Lebrin F, et al. Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest,2005,128(6 Suppl):585S-590S.
[62]Goumans MJ, Lebrin F, Valdimarsdottir G. Controlling the angiogenic switch: abalance between two distinct TGF-b receptor signaling pathways. Trends Cardiovasc Med,2003,13(7):301-307.
[63]Bertolino P, Deckers M, Lebrin F, et al. Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest, 2005, 128(6 Suppl):585S-590S.
[64]Holderfield MT, Hughes CC. Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-beta in vascular morphogenesis. Circ Res, 2008, 102(6) :637-652.
[65]van Meeteren LA, Goumans MJ, ten Di jke P. TGF-β receptor signaling pathways in angiogenesis; emerging targets for anti-angiogenesis therapy. Curr Pharm Biotechnol, 2011, 12(12):2108-2120.
[66]Xin X, Yang S, Ingle G, et al. Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Am J Pathol, 2001, 158(3) : 1111-1120.
[67]Sengupta S, Sellers LA, Gherardi E, etal. Nitric oxide modulates hepatocyte growth factor/scatter factor-induced angiogenesis. Angiogenesis, 2004, 7(4) : 285-294.
[68]Kaga T, Kawano H, Sakaguchi M, et al. Hepatocyle growth factor stimulated angiogenesis without inflammation: Differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor. Vascul Pharmacol, 2012, 57(1):3-9.
[69]Freret T,Valable S,Chazalviel L, et al. Delayed administration of deferoxamine reduces brain damage and promotes functional recovery after transient focal cerebralischemiainthe rat.Eur J Neurosci,2006, 23(7) : 1757-1765.
[70]Iwai M, Cao G, Yin W, et al. Ery thropoiet i n promotes neuronal replacement through revascularizalion and neurogenesis after neonatal hypoxia/ischemia in rats. Stroke, 2007, 38(10) :2795-2803.
[71]Semen/a GL, Shimoda LA, Prabhakar NR. Regulat ion of gene expression by HIF-1. Novartis Found Symp, 2006, 272:2-8.
[72]May D, Itin A, Gal 0, Kalinski H, et al. Erol-L alpha plays a key role in a MIF01-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer. Oncogene, 2005, 24(6): 1011-1020.
[73]Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci, 2004, 5(6): 437-448.
[74]Semenza GL. Angiogenesis in ischemic and neoplastic disorders. Ann Rev Med, 2003,54:17-28.
[75]Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med,2002,8(8):495-505.
[76]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol,2000,156(3):965-976.
[77]Sasabe E, Tatemoto Y, Li D, et al. Mechanism of HIF-lalpha-dependent suppression of hypoxia-induced apoptosis insquamous cell carcinoma cells. Cancer Sci,2005,96(7):394-402.
[78]Li J, Zhang X, Se jas DP, et al. Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. J Biol Chem,2004,279(40):41275-41279.
[79]Carmeliet P, Dor Y, Herbert JM, et al. Role of HIF-lalpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature,1998, 394(6692):485-490.
[80]Ribatti D, Vacca A, Roccaro AM, et al. Erythropoietin as an angiogenic factor. Eur J Clin Invest,2003,33(10):891-896.
[81]Li F, Chong ZZ, Maiese K. Erythropoietin on a tightrope:balancing neuronal and vascular protection between intrinsic and extrinsic pathways. Neurosignals, 2004,13(6):265-289.
[82]Bernaudin M, Marti HH, Roussel S, et al. A potential rolefor erythropoietin in focal permanent cerebral ischemia in mice.J Cereb Blood Flow Metab, 19(6)643-651.
[83]Holstein JH, Orth M, Scheuer C, et al. Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in a femoral segmental defect model in mice. Bone,2011,49(5):1037-1045.
[84]Beck H, Voswinckel R, Wagner S, et al. Participation of bone marrow-derived cells in long-term repair processes after experimental stroke. J Cereb Blood Flow Metab,2003,23(6):709-717.
[85]Sobrino T, Hurtado 0, Moro MA, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke,2007,38(10):2759-1764.
[86]Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke,2008, 39(1):69-74.
[87]Fan Y, Shen F, Frenzel T, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol,2010,67(4):488-497.
[88]王宇,马淑兰,崔建美,等.针刺抗哮喘大鼠血清差异组份的色谱分析.上海针灸杂志,2006,25(8)：41-43.
[89]Wang Yu, Yang Yong qing, MA Shu Ian, et al. SDS-PAGE analysis of components in serum with anti-asthma activity derived from rats treated by acupuncture. J Acupuncture Tuina Sci,2009,7:8-12.
[90]陈云飞,杨文佳,马晓芃,等.不同时段艾灸血清中内生性蛋白组分双向电泳的实验研究.上海中医药大学学报,2007,21(2)：57-60.
[91]王素娥,彭争荣,钟广伟,等.针刺血清对脑源性神经干细胞分化的影响.中国康复医学杂志,2007,22(5)：459-460.
[92]Dunning MD, Lakatos A, Loizou L, et al. Superparamagnetic i ronoxide-labeled schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS. Neurosci,2004,24(44):9799-9810.
[93]秦逸人,赵英侠.针灸治疗骨质疏松的临床与实验研究新进展.中医杂志,2005,46(增刊)：306.
[94]赵英侠,王静,秦逸人,等.针刺血清对体外培养破骨细胞数量的影响.中国针灸,2007,27(7)：521-524.
[95]赵英侠,王静,秦逸人,等.经针刺去除卵巢大鼠血清对体外培养破骨细胞骨吸收功能的影响.中国康复医学杂志,2008,23(5)：420-422.
[96]宋秀娟,陈晞,汪洋,等.兔胸段脊髓损伤后不同组穴的针刺血清对体外脊髓神经元生长的影响.宁夏医学杂志,2009,31(2)：133-135.
[97]罗明富,李翠红,张金铃,等.针刺血清降低大鼠培养心肌细胞内Ca2+含量的研究.中国针灸,2006,26(5)：367-369.
[98]罗明富,李翠红,张金铃,等.针刺血清对培养心肌细胞线粒体功能影响的观察.针刺研究,2005,30(3)：153-154.
[99]李瑞午,张静龄,郭莹,等.针刺血清对体外培养神经细胞内钙离子浓度的影响.中西医结合学报,2004,2(6)：453-455.
[100]邓元江,易受乡,严洁,等.促阳明经穴针刺血清对家兔离体胃窦平滑肌细胞舒缩活动的影响.中医杂志,2005,46(4)：264-266.
[101]邓元江,易受乡,严洁,等.足阳明经穴针刺血清对家兔离体胃窦平滑肌细胞内 钙离子浓度影响的实验研究.新中医,2005,37(10)：91-93.
[102]邰浩清,周春祥,姜文芳.针刺动物血清对内耳干细胞分化影响的实验研究.南京中医药大学学报,2009,25(5)：367-369.
[103].Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science,1997,275 (5302):964-977.
[104]Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological andpathological neovascularization. Circ Res,1999,85(3):221-228.
[105]Risau W, Flamme I. Vaseulogenesis. Ann Rev Cell Dev Biol,1995,11 (9):79-91 106 Folkman J, Shing Y. Angiogenesis. Boil Chem,1992,267(16):10931-10934.
[107]Suda T, Takakura N, Oike Y. Hematopoiesis and angiogenesis. Int J Hematol, 2000,71(2):99-107.
[108]Urbich C, Dimmeler S. Endothelial progenitor cells:characterization and role in vascularbiology. Circ Res,2004,95(4):343-353.
[109]Asahara T, Kawamoto A, Masuda H. Concise review:Circulating endothelial progenitor cells for vascular medicine. Stem Cells,2011,29(11):1650-1655.
[110]Lin Y, Weisdorf D, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest,2000,105(1):71-77.
[111]Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood,1998,92(2):362-367.
[112]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24(2):288-293.
[113]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[114]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24(2):288-293.
[115]Sieveking DP, Buckle A, Celermajer DS, et al. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations:insights from a novel human angiogenesis assay. J Am Coll Cardiol,2008,51(6):660-668.
[116]Aicher A, Rentsch M, Sasaki K, et al. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res, 2007, 100(4):581-589.
[117]Wojakowski W, Kucia M, Kazmierski M, et al. Circulating progenitorcells in stable coronary heart disease and acute coronary syndromes: Relevant reparatory mechanism?. Heart, 2008, 94 (1):27-33.
[118]Losordo DW, Kishore R. A big promise from the very small identification of circulating embryonic stem-like pluripotent cells in patients with acute myocardial infarction.J Am Coll Cardiol, 2009, 53(1):10-12.
[119]Umemura T, HigashiY. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci, 2008, 108(1):1-6.
[120]Ding H, Triggle CR. Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium. Vasc Heal th Risk Manag, 2005, 1(1):55-71.
[121]Caballero S, Sengupta N, Afzal A, et al. Ischcmic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes, 2007, 56(4) : 960-967.
[122]Shi Q, Raf i i S, Wu MH, et al. Evidence for eirculat ing bonemarrow-derived endolhelial cells. Blood, 1998, 92(2):362-367.
[ 123]Garcia-Barros M, Paris P, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis.Science,2003, 300(5622):1155-1159.
[124]Casamassimi A, Balestrieri ML, Fiorito C, et al. Comparison between total endothelial progenitor cell isolation versus enriched Cd133+ culture. J Biochem, 2007, 141(4) : 503-511.
[125]Nakahata T, Ogawa M. Hemopoietic colony-forming cells in umbilical cord blood wi th extensive capabi 1 i ty to generate mono- and mul tipotent ial hemopoietic progenitors. J Clin Invest, 1982, 70(6):1324-1328.
[ 126]Mayani II, Lansdorp PM. Thy—1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human urnbilical cord blood. Blood, 1994, 83(9) :2410-2417.
[127]Murohara T, Ikeda II, Duan J, et al. Transplanted cord blood-derived endothelial precursor colls augment postnalal neovascularization. J Clin Invest, 2000, 105(11): 1527-1536.
[128]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[129]Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies. Tissue Eng,2001,7(2):211-228.
[130]Planat-Benard V, Silvestre JS, Cousin B, et al. Plasticity of human adipose lineage cells toward endothelial cells:physiological and therapeutic perspectives. Circulation,2004,109(5):656-663.
[131]Miranville A, Heeschen C, Sengenes C, et al. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation, 2004,110(3):349-55.
[132]周秀娟.人外周血、脐血、脂肪组织中内皮祖细胞生物特性比较研究.中国动脉硬化杂志,2008,19(8)：675-679.
[133]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003,93(2):e17-24.
[134]Tamaki T, Akatsuka A, Ando K, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol, 2002,157(4):571-577.
[135]Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell,2003,114(6):763-776.
[136]Cherqui S, Kurian SM, Schussler O, et al. Isolation and angiogenesis by endothelial progenitors in the fetal liver. Stem Cells,2006,24(1):44-54.
[137]Hirschi KK, Goodell MA. llematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Ther,2002,9(10):648-652.
[138]Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood,2000, 95(10):3106-3112.
[139]Harraz M, Jiao C, Hanion HD, et al. CD34-blood-derived human endothelial cells progenitors. Stem Cells,2001,19(4):304-312.
[140]Shintani S, Murohara T, Ikeda H, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation, 2001,103(6):897-903.
[141]Li L, Xie T. Stem cell niche:structure and function. Annu Rev Cell Dev Biol,2005,21:605-631.
[142]Yin T, LiL The stem cell niches in bone. J Clin Invest, 2006, 116(5): 1195-1201.
[143]Shepherd RM, Capoccia BJ, Devine SM, et al. Angiogenic cells can be rapidly mobilized and efficiently harvestedfrom the blood following treatment with amd3100. Blood, 2006, 108:3662-3667.
[144]Ramirez P, Rettig MP, Uy GL, et al. BI05192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem andprogenitor cells. Blood, 2009, 114:1340- 1343.
[145]Walter DH, Rochwalsky U, Reinhold J, et al. Sphingosine-1-phosphate stimulates the functional capacity ofprogenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arterioscler Thromb Vasc Biol, 2007, 27(2):275-282.
[146]Sumi M, Sata M, Miura S, et al. Reconstituted high-density lipoprotein stimulates differentiation ofendothelial progenitor cells and enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol, 2007, 27(4) 813-818.
[147 ]Murayama T, Topper OM, Silver M, et al. Determination of bone marrow-derived endothelialprogenitor cellsignificancein angiogenic growthfactor-inducedneovascularizationinvivo.ExpHomatol,2002, 30(8) : 967-972.
[148]Hiasa K, Ishibashi M,Ohtani K, et al. Gene transfer of stromal cell-derivedfactor-lalpha enhances ischemia vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation, 2004, 109 (20) :2454-2461.
[149]Zeng L, Xiao Q,Margariti A, et al. IIDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. J Cell Biol, 2006, 174(7):1059-1069.
[150]Jie KE, Goossens MH, van Oostrom 0, et al. Circulating endothelial progenitor cell levels are higher during childhood than in adult life. Atherosclerosis, 2009, 202(2):345-347.
[151]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity ofcirculating endothelial progenitor cells inversely correlate with risk factors forcoronary artery disease. Circ Res,2001,89(1):El-7.
[152]Heiss C, Keymel S, Niesler U, et al. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol,2005, 45(9):1441-1448.
[153]Kushner EJ, Van Guilder GP, Maceneaney OJ, et al. Aging and endothelial progenitor cell telomere length in healthy men. Clin Chem Lab Med,2009, 47(1):47-50.
[154]He T, Joyner MJ, Katusic ZS. Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells. Microvasc Res, 2009,78(3):447-452.
[155]Thum T, Hoeber S, Froese S, et al. Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulinlike growth-factor-1. Circ Res,2007,100(3):434-443.
[156]Hoetzer GL, Van Guilder GP, Irmiger HM, et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. J Appl Physiol,2007,102(3):847-852.
[157]Chang EI, Loh SA, Ceradini DJ, et al. Age decreases endothelial progenitor cellrecruitment through decreases in hypoxia-inducible factor lalpha stabilization during ischemia. Circulation,2007,116(24):2818-2829.
[158]Hoetzer GL, MacEneaney OJ, Irmiger HM, et al. Gender differences in circulatingendothelial progenitor cell colony-forming capacity and migratory activity inmiddle-aged adults. Am J Cardiol,2007,99(1):46-48.
[159]Fadini GP, de Kreutzenberg S, Albiero M, et al. Gender differences in endothelial progenitor cells and cardiovascular risk profile:the role of female estrogens. Arterioscler Thromb Vasc Biol,2008,28(5):997-1004.
[160]Stauffer BL, Maceneaney OJ, Kushner EJ, et al. Gender and endothelial progenitor cell number in middle-aged adults. Artery Res,2008,2(4):156-160.
[161]Fadini GP, de Kreutzenberg S, Albiero M, et al. Gender differences in endothelial progenitor cells and cardiovascular risk profile:the role of female estrogens. Arterioscler Thromb Vasc Biol,2008,28(5):997-1004.
[162]Imanishi T, Hano T, Nishio I. Estrogen reduces angiotensin Ⅱ-induced acceleration of senescence in endothelial progenitor cells. Hypertens Res,2005, 28(3):263-271.
[163]Bogdanski P, Miller-Kasprzak E, Pupek-Musialik D, et al. Evaluation of Endothelial progenitor cells in patients with hypertension:Pp.6.248. J Hypertens,2010,28:pe124.
[164]Georgescu A, Alexandru N, Andrei E, et al. Circulating microparticles and endothelial progenitor cells in atherosclerosis:pharmacological effects of irbesartan. J Thromb Haemost,2012,10(4):680-691.
[165]Dernbach E, Randriamboavonjy V, Fleming I, et al. Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors. Basic Res Cardiol,2008,103(6):572-581.
[166]Alexandru N, Popov D, Dragan E, et al. Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia. PLoS One,2013,8(1):e52058.
[167]Min TQ, Zhu CJ, Xiang WX, et al. Improvement in endothelial progenitor cells from peripheral blood by ramipril therapy in patients with stable coronary artery disease. Cardiovasc Drugs Ther,2004,18(3):203-209.
[168]Yu Y, Fukuda N, Yao EH, et al. Effects of an ARB on endothelial progenitor cell function and cardiovaseular oxidation in hypertension. Am J Hypertens,2008, 21(1):72-77.
[169]Menegazzo L, Albiero M, Avogaro A, et al. Endothelial progenitor cells in diabetes mellitus. Biofactors,2012,38(3):194-202.
[170]Topper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells fromtype Ⅱ diabetics exhibit impaired proliferation, adhesion, and incorporation intovascular structures. Circulation,2002,106(22):2781-2786.
[171]Voo S, Dunaeva M, Eggermann J, et al. Diabetes mellitus impairs CD133+ progenitor cell function after myocardial infarction. J Intern Mod,2009, 265(2):238-249.
[172]Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction:a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes,2004,53(1):195-199.
[173]Hamed S, Brenner B, Aharon A, et al. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus. Cardiovasc Diabetol,2009,8:56.
[174]Kuki S, Imanishi T, Kobayashi K, et al. Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J,2006,70(8):1076-1081.
[175]Rosso A, Balsamo A, Gambino R, et al. p53 Mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes. J Biol Chem,2006, 281(7):4339-4347.
[176]Zhang W, Wang X, Jin H, et al. Effects of high glucose plus high insulin on proliferation and apoptosis of mouse endothelial progenitor cells. Inflamm Res,2008,57(12):571-576.
[177]Jung C, Rafnsson A, Shemyakin A, et al. Different subpopulations of endothelial progenitor cells and circulating apoptotic progenitor cells in patients with vascular disease and diabetes. Int J Cardiol,2010, 143(3):368-372.
[178]Chen YH, Lin SJ, Lin FY, et al. High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes,2007,56(6):1559-1568.
[179]Bhatwadekar AD, Glenn JV, Li G, et al. Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells:implications for vasodegeneration in diabetic retinopathy. Invest Ophthalmol Vis Sci,2008, 49(3):1232-1241.
[180]Urbich C, Dernbach E, Rossig L, et al. High glucose reduces cathepsin L act ivi ty and impairs invasion of circulating progenitor cells. J Mol Cell Cardiol, 2008,45(3):429-436.
[181]Liang C, Ren Y, Tan H, et al. Rosigl i tazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products. Br J Pharmacol,2009,158(8):1865-1873.
[182]Chen Q, Dong L, Wang L, et al. Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2. Biochem Biophys Res Commun,2009,381(2):192-197.
[183]Shen C, Li Q, Zhang YC, et al. Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways. Biomed Pharmacother,2010,64(1):35-43.
[184]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors forcoronary artery disease. Circ Res,2001,89(1):E1-7.
[185]Ma FX, Zhou B, Chen Z, et al. Oxidized low density lipoprotein impairs endothelial progeni tor cells by regulation of endothelial nitrie oxide synthase. J Lipid Res, 2006, 47(6) : 1227-1237.
[186]Petoumenos V, Nickenig G, Werner N. High density lipoprotein exerts vasculoprotection via endothelial progenitor cells. J Cell Mol Med, 2009, 13(11-12):4623-4635.
[187]Noor R, Shuaib U, Wang CX, et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis, 2007, 192(1):92-99.
[188]Sobrino T, Blanco M, Perez-Mato M, et al. Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase. Eur J Neurol, 2012, 19(12):1539-1546.
[189]MacEneaney 0J, Kushner EJ, Van Guilder GP, et al. Endothelial progenitor cell number and colony-forming capacity in overweight and obese adults. Int J Obes(Lond), 2009, 33(2):219-225.
[190]Maceneaney OJ, Kushner EJ, Westby CM, et al. Endothelial progenitor cell function, apoptosis, and telomere length in overweight/obese humans. Obesity(Silvor Spring), 2010, 18(9):1677-1682.
[191]Westerweel PE, Visseren FL, Hajer GR, et al. Endothelial progenitor cell levels in obese men with the metabolic syndrome and the effect of simvastat in monotherapy vs. simvastatin/ezetimibe combination therapy. Eur Heart J, 2008, 29(22) : 2808-2817.
[192]Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 2004, 364(9438):937-952.
[193]Kondo T, Hayashi M, Takeshita K, et al. Smoking cessation rapidly increasescirculating progenitor cells in peripheral blood in chronic smokers. Arteriosc lerThromb Vasc Biol, 2004, 24(8): 1442-1447.
[194]Michaud SE, Dussault S, Haddad P, et al. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis, 2006, 187(2):423-432.
[195]van Grevenynghe J, Monteiro P, Gilot D, et al. Human endothelial progenitors constitute targets for environmental atherogenic polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun, 2006, 341 (3) :763-769.
[196]Fujioka D, Kawabata K, Saito Y, et al. Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression ininfarcted heart. Am J Physiol Heart Circ Physiol,2006, 290(6):H2409-2416.
[197]Sugimoto A, Masuda H, Eguchi M, et al. Nicotineenlivenment of blood flow recovery following endothelial progenitor cell transplantation into ischemic hindlimb. Stem Cells Dev,2007,16:649-656.
[198]Heiss C, Amabile N, Lee AC, et al. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function:sustained vascular injury and blunted nitric oxide production. J Am Coll Cardiol,2008, 51 (18):1760-1771.
[199]Masuda H, Kalka C, Takahashi T, et al. Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res,2007,101 (6):598-606.
[200]Bauer SM, Goldstein LJ, Bauer RJ, et al. The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia. J Vase Surg,2006,43(1):134-141.
[201]Iwakura A, Shastry S, Luedemann C, et al. Estradiol enhances recovery after myocardial infarction by augmenting incorporation of bone marrow-derived endothelial progenitor cells into sites of ischemia-induced neovascularization via endothelial nitric oxide synthase-mediated activation of matrix metalloproteinase-9. Circulation,2006,113(12):1605-1614.
[202]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30(8):967-972.
[203]Masuda 11, Kalka C, Takahashi T, et al. Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res,2007,101 (6):598-606.
[204]Ii M, Nishimura H, Iwakura A, et al. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation, 2005,111(9):1114-1120.
[205]Miyamoto Y, Suyama T, Yashita T, et al. Bone marrow subpopulations contain distinct types of endothelial progenitor cells and angiogenic cytokine-producing cells. J Mol Cell Cardiol, 2007, 43(5):627-635.
[206]Jujo K,li M,Losordo DW.Endothelial progenitor cells in neovascularization of infarcted myocardium.J Mol Cell Cardiol,2008, 45(4) : 530-544.
[207]Kawamoto A,Tkebuchava T, Yamaguchi J, et al.Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation, 2003, 107(3):461-468.
[208]Kalka C, Masuda H,Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA, 2000, 97(7):3422-3427.
[209]Hess DC, Hill WD, Martin-Studdard A, et al. Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke. Stroke, 2002, 33(5) : 1362-1368.
[210]Wu X, Rabkin-Aikawa E, Guleserian KJ, et al. Tissue engineered microvossels on three-dimensional biodegradable scaffolds using human endothel ial progenitor cells. Am J Physial Heart Circ Physiol, 2004, 287(2):480-487.
[211]Shirota T, Yasu i H, Shimokawa H, et al. Fabrication of endothelial progenitor coll (EPC) -seeded intravascular stent devices and invitro endothelialization on hybrid vascular tissue. Biomaterials, 2003, 24(13) : 2295-2302.
[212]Taguchi A,Matsuyama T,Moriwaki H, et. al. Circulating CD34-positive cells provide an index of cerebrovascular function. Circulation, 2004, 109(24):2972-2975.
[213]Ghani U, Shuaib A, Salam A, et al. Endothelial progenitor cells during cerebrovascular disease. Stroke, 2005, 36(1):151-153.
[214]Fadini GP, Coracina A, Baesso I, et al. Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke, 2006, 37(9):2277-2282.
[215]Chu K,Jung KH, Lee ST, et al. Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke. Stroke, 2008, 39(5) : 1441-1447.
[216]Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke, 2008, 39(1):69-74.
[217]Sobrino T, Hurtado 0, Moro MA, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke,2007,38(10):2759-2764.
[218]Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest, 2004,114(3):330-338.
[219]Morgan R, Kreipke CW, Roberts G, et al. Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis. Neurol Res,2007,29(4):375-381.
[220]Brea D, Rodriguez-Gonzalez R, Sobrino T, et al. Proteomic analysis shows differential protein expression in endothelial progenitor cells between healthy subjects and ischemic stroke patients. Neurol Res,2011,33(10):1057-1063.
[221]Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem cell reviews,2011,7(1):208-220.
[222]Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics--2008 update:a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation,2008,117(4): e25-146.
[223]Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update:a report from the American Heart Association. Circulation,2013,127(1):e6-e245.
[224]American Heart Association. Heart disease and stroke statistics--2005 Update. Dallas, Texas:American Heart Association,2005.
[225]Roger VL, Go AS, Lloyd-Jones DM, et al. Heart diseas and stroke statistics-2012 update:a report from the American Heart Association. Circulation,2012, 125(1):e2-e220.
[226]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30(8):967-972.
[227]刘轲,李建生,周友龙,等.脑脉通对老龄大鼠脑缺血/再灌注微血管生成及bFGF. TGF表达的影响.中华中医药杂志(原中国医药学报),2010,25(8)：1188-1192.
[228]Belayev L, Endres M, Prinz V, et al. Focal cerebral ischemia in the mouse and rat using the intraluminal suture-filament model. Neuromethods,2010, 47:29-40
[229]Aspey BS, Cohen S, Patel Y, et al. Middle cerebral artery occlusion in the rat:consistent protocol for a model of stroke. Neuropathol Appl Neurobiol, 1998,24(6):487-497.
[230]Oliff HS, Coyle P, Weber E. Rat strain and vendor differences in collateral anastomoses. J Cereb Blood Flow Metab,1997,17:571-578.
[231]Bardutzky J, Shen Q, Henninger N, et al. Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging. Stroke, 2005,36(9):2000-2005.
[232]Encarnacion A, Horie N, Keren-Gill H, et al. Long-term behavioral assessment of function in an experimental model for ischemic stroke.2011, 196(2):247-257.
[233]龚彪,李长清,黄剑.SD大鼠线栓法局灶性脑缺血/再灌注模型的改进.重庆医学,2006,35(4)：313-315.
[234]Alkayed NJ, Harukuni I, Kimes AS, et al. Gender-linked brain injury in experimental stroke. Stroke,1998,29(1):159-165.
[235]Saltiki K, Alevizaki M. Coronary heart disease in postmenopausal women; therole of endogenous estrogens and their receptors. Hormones(Athens),2007, 6(1):9-24.
[236]Plamondon H, Morin A, Charron C. Chronic 17beta-estradiol pretreatment and ischemia-induced hippocampal degeneration and memory impairments:a 6-month survival study. Horm Behav,2006,50(3):361-369.
[237]Wang LC, Futrell N, Wang DZ, et al. A reproducible model of middle cerebral infarcts, compatible with long-term survival, in aged rats. Stroke,1995, 26(11):2087-2090.
[238]文灿,朱星红.大鼠大脑中动脉的衰老性变化.解剖学杂志,2004,27(5)：528
[239]谢宁,段新芬,牛英才.线栓法制备大鼠大脑中动脉脑缺血动物模型影响因素探析.中医药管理杂志,2006,14(12)：51.
[240]赵帅,樊小农,孟智宏,等.线栓法制备大鼠中动脉缺血闭塞模型研究进展.江西中医药,2012,43(351)：77-80
[241]许天新,蔡德雷,郑云燕,等.4-8周龄SD大鼠体重和主要脏器正常参考值.浙江预防医学,2006,18(8)：73-75
[242]Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev,2012, 1:CD003435.
[243]吴忧,贾建平.脑缺血动物模型的制备及影响因素.中国脑血管病杂志,2007,4(1)： 42-44
[244]Koizumi J, Yoshida Y, Nazawa T, et al. Experimental studies of ischemia brain edema,1:A new experimental model of cerebral embolism infarcts in the ischemia area. Stroke,1986, (8):1-8.
[245]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke,1989,20(1):84-91
[246]Wiedlocha A, S(?)rensen V. Signaling, internalization, and intracellular activity of fibroblast growth factor.Curr Top Microbiol Immunol,2004, 286:45-79.
[247]FolkmanJ, KlagsbrumM. Angiogenic factors. Science,1987,235:442-447
[248]Damico FM. Angiogenesis and retinal diseases. Arq BrasOftlmol,2007, 70(3):547-553
[249]Bottcher RT, Niehrs C. Fibroblast growth factor signaling during early vertebrate development. Endocr Rev,2005,26(1):63-77.
[250]Stavri GT, Zachary IC, Baskerville PA, et al. Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle colls. Synergistic interaction wi th hypoxia. Circulation, 1995,92(1):11-14
[251]Asahara T, Bauters C, Zheng LP, et al. Synergistic effect of vascular endothelial growth factorand basic fibroblast growth factor on angiogenesis in vivo. Circulation,1995,92(9 Suppl):11365-371.
[252]Koivisto H, Hyvarinen M, Stromberg AM, et al. Cultures of human embryonic stem cells:serum replacement medium or serum-containing media and the effect of basic fibroblast growth factor. Reprod Biomed Online,2004,9(3):330-337
[253]Sun XT, Ding YT, Yan XG, et al. Angiogenic synergistic effect of basic fibroblast growth factor and vascular endothelialgrowthfactorin an in vitro quantitative microcarrier-based three-dimensional fibrin angiogenesis system. World J Gastroenterol,2004,10(17):2524-2528.
[254]Akasaka Y, Ono I, Yamashita T, et al. Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds. J Pathol,2004,203(2):710-720.
[255]Doi K, Ikeda T, Marui A, et al. Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischaemia. Heart Vessels,2007,22:104-108.
[256]Cao Y, Cao R, Hedlund EM. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med (Berl),2008, 86(7):785-789.
[257]Mavria G, Vercoulen Y, Yeo M, et al. ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell,2006,9(1):33-44.
[258]Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci,2001,22(4):201-207.
[259]Maffucci T, Raimondi C, Abu-Hayyeh S, et al. A phosphoinositide 3-kinase/phospholipase Cgammal pathway regulates fibroblast growth factor-induced capillary tube formation. PLoS One,2009,4(12):e8285.
[260]Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res,2007,100(6):782-794.
[261]Li S, Huang NF, Hsu S. Mechanotransduction in endothelial cellmigration. J Cell Biochem,2005,96(6):1110-1126.
[262]徐彬,武晓英,林桂先,等.bFGF基因转染对血管内皮细胞迁移的影响及机制.山东医药,2010,(11)：21-24
[263]Shi C, Lu J, Wu W, et al. Endothelial cell-specific molecule2 (ECSM2) localizes to cell-cell junctions and modulates bFGF-directed cell migration via the ERK-FAKpathway. PLoS One,2011,6(6):e21482.
[264]Rafat N, Beck Gch, Pean-Tapia PG, et al. Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease. Stroke,2009, 40(2):432-438.
[265]Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat.1995,36(2):169-180.
[266]Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol,1995,147(1):9-19.
[267]Mahzouni P, Mohammadizadeh F, Mougouei K, et al. Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor Ⅷ-related antigen" (von Willebrand factor) expression in tumor microvessels. Indian J Pathol Microbiol,2010, 53(4):605-610.
[268]Horak ER, Leek R, Klenk N, et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet,1992,340(8828):1120-1124.
[269]da Silva BB, Lopes-Costa PV, dos Santos AR, et al. Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer. Eur J Gynaecol Oncol,2009,30(3):285-288.
[270]Ahrens I, Domeij H, Topcic D, et al. Successful in vitro expansion an differentiation of cord blood derived CD34+ cells into early endothelial progenitor cells reveals highly differential gene expression. PLoS One,2011, 6(8):e23210.
[271]Thill M, Strunnikova NV, Berna MJ, et al. Late outgrowth endothelial progenitor cells in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci,2008,49(6):2696-2708.
[272]UmemuraT, HigashiY. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci,2008,108(1):16.
[273]Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science,2003, 300(5622):1155-1159.
[274]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[275]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003,93(2):e17-24.
[276]Cherqui S, Kurian SM, Schussler 0, et al. Isolation and angiogenesis by endothelial progenitors in the fetal liver. Stem Cells,2006,24(1):44-54.
[277]Casamassimi A, Balestrieri ML, Fiorito C, et al. Comparison between total endothelial progenitor cell isolation versus enriched Cd133+ culture. J Biochem, 2007,141(4):503-511.
[278]Kahler CM, Wechselberger J, Hilbe W, et al. Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury. Respir Res,2007,8:50.
[279]Chen YH, Lin SJ, Lin FY, et al. High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes,2007,56(6):1559-1568.
[280]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24:288-293.
[281]Peichev M, Naiyer AJ, PereiraD, et al. Expression of VEGFR-2 and AC133 by circulating human CD34 (+) cells identifies a population of functional endothelial precursors. Blood,2000,95(3):952-958.
[282]Yoder MC. Defining human endothelial progenitor cells. J Thromb Haemost. 2009,7 Suppl 1:49-52.
[283]Dimmeler S. Regulation of bone marrow-derived vascular progenitor cell mobilization and maintenance. Arterioscler Thromb Vase Biol.2010,30(6): 1088-1093.
[284]Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood,1997,90(12):5002-5012.
[285]Leone AM, Valgimigli M, Giannico MB, et al. From bone marrow to the arterial wall:the ongoing tale of endothelial progenitor cells. Eur Heart,2009, 30(8):890-899.
[286]Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol,2004,287(3):C572-579.
[287]Mizrak D, Brittan M, Alison M. CD133:molecule of the moment. J Pathol. 2008,214(1):3-9.
[288]Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene,2000, 19(49):5598-5605.
[289]Timmermans F, Plum J, Yoder MC, et al. Endothelial progenitor cells: identity defined?. J Cell Mol Med,2009,13(1):87-102.
[290]Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood, 2007,109(5):1801-1809.
[291]Hirschi KK, Ingram DA, Yoder MC, et al. Assessing identity, phenotype, and fate of endothelial progenitorcells. Arterioscler Thromb Vasc Biol,2008, 28(9):1584-1595.
[292]Yoder MC. Defining human endothelial progenitor cells. J Thromb Haemost, 2009, Suppl 1:49-52.
[293]Johansson CB, Momma S, Clarke DL, et al. Identification of a neural stem cell in the adult mammalian central nervoussystem. Cell,1999,96(1):25-34.
[294]Mothe AJ, Tator CH. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neurosci ence,2005,131(1):177-187.
[295]Meng QY, Li XQ, Yu XB, et al. Transplantation of VEGF165-gene-transfected endothelial progenitor cells in the treatment of chronic venous thrombosis in rats. Chin Med J(Engl),2010,123(4):471-477.
[296]Voyta JC, Via DP, Butterfield CE, etal. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol,1984,99(6):2034-2040.
[297]方立建.人脐带血内皮祖细胞的培养与鉴定.长春：吉林大学,2008.
[298]Yang C, Zhang ZH, Li ZJ, et al. Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation. Thromb Haemost,2004,91 (6):1202-1212.
[299]Holthofer H, Virtanen I, Kariniemi AL, etal. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest,1982, 47(1):60-66.
[300]Suzuki K, Sakata N, Kitani A, et al. Characterization of human monocytic cell line, U937, in taking up acetylated low-density lipoprotein and cholesteryl ester accumulation. A flow cytometric and HPLC study. Biochim Biophys Acta,1990, 1042(2):210-216.
[301]Urbich C, Heeschen C, Aicher A, et al. Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells. Circulation,2003,108(20):2511-2516.
[302]Rohde E, Malischnik C, Thaler D, et al. Blood monocytes mimic endothelial progenitor cells. Stem Cells,2006,24(2):357-367.
[303]Graziano M, St-Pierre Y, Potworowski EF. UEA-I-binding to thymic medullary epithelial cells selectively reduces numbers of cortical TCRalphabeta+ thymocytes in FTOCs. Immunol Lett,2001,77(3):143-150.
[304]Liu SM, Li CY. Immunohistochemical study of Ulex europaeus agglutinin 1(UEA-1) binding of megakaryocytes in bone marrow biopsy specimens: demonstration of heterogeneity in staining pattern reflecting the stages of differentiation. Hematopathol Mol Hematol,1996,10(1-2):99-109.
[305]Barsotti MC, Magera A, Armani C, et al. Fibrin acts as biomimetic niche inducing both differentiation and stem cell marker expression of early human endothelial progenitor cells. Cell Prolif,2011,44(1):33-48.
[306]施森,何延政,宋丽,等.血管内皮生长因子在鼠尾胶原凝胶诱导三维血管新生中的作用研究.2010;14(16)：2879-2882.
[307]AsaharaT, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res,1999,85(3):221-228.
[308]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003(1),93:e17-e24.
[309]Morgan R, Kreipke CW, Roberts G, et al. Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis. Neurol Res,2007,29(4):375-381.
[310]Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem Cell Rev, 2011,7(1):208-220.
[311]Umemura T, Higashi Y. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci,2008,108(1):1-6.
[312]Su Y, Zheng L, Wang Q, et al. The PI3K/Akt pathway upregulates Idl and integrin a 4 to enhance recruitment of human ovarian cancer endothelial progenitor cells. BMC Cancer,2010,10:459.
[313]Gao D, Nolan DJ, Mellick AS, et al. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science,2008,319(5860): 195-198.
[314]王秀志,张莉,蔡绍皙,等.电针对脑缺血再灌注大鼠缺血局部脑血管形成的影响.针灸临床杂志,2010,26(08)：61-63.
[315]黄帝内经素问[M].北京：中医古籍出版社,1997：52.
[316]明·杨继洲原著.靳贤补辑重编.黄龙祥整理.针灸大成[M].北京：人民卫生出版社,2007：387.
[317]清·吴亦鼎撰.阎寿峰初校.神灸经纶.北京：人民卫生出版社,1983：81.
[318]Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium. Circulation,1986,74 (5):1124-136.
[319]Szekeres L. Drug-induced delayed cardiac protection against the effects of myocardial ischemia. Pharmacol Ther,2005,108(3):269-280.
[320]钟旭,潘珊珊.运动预适应对大鼠急性心肌缺血损伤早期保护作用的研究.中国运动医学杂志,2009,28(3)：262-266.
[321]Liebelt B, Papapetrou P, Ali A, et al. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience,2010, 166(4):1091-1100.
[322]Gross GJ. Remote preconditioning and delayed cardioprotection in skeletal muscle. Am J Physiol Regul Integr Comp Physiol,2005,289(6):R1562-1563.
[323]Meybohm P, Zacharowski K, Cremer J, et al. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial-the RIPHeart-Study. Eur Heart J,2012, 33(12):1423-1426.
[324]Khaliulin I, Clarke SJ, Lin H, et al. Temperature preconditioning of isolated rat hearts--a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore. J Physiol,2007,581(Pt3):1147-1161.
[325]熊英,顾一煌,吴云川.针灸预处理的心肌保护研究进展及应用前景.中国运动医学杂志,2012,31(10)：926-930.
[326]李晓泓,张露芬,解秸萍.针灸预处理的研究概况与思考.中国临床康复,2005,9(25)：186-187.
[327]崔丽,孙国杰,周华,等.针灸预刺激对阿尔茨海默病模型大鼠学习记忆能力及海马区SOD和NOS的影响.湖北中医学院学报,2009,11(3)：6-8.
[328]柯红,孙国杰,周华.针灸预刺激对AD大鼠脑内自由基影响的实验研究.湖北中医学院学报,2009,11(2)：14-16.
[329]豁银成,孙国杰,杜艳军.针灸预刺激对AD大鼠神经元凋亡相关蛋白Bcl-2、NF-κB的影响.湖北中医学院学报,2010,12(2)：16-18.
[330]Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med,2003, 348(7):593-600.
[331]Galimi F, Summers RG, van Praag H, et al. A role for bone marrow-derived cells in the vasculature of noninjured CNS. Blood,2005,105(6):2400-2402.
[332]Zhang ZG, Zhang L, Jiang Q, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res,2002,90(3):284-288.
[2]Baron JC. Perfusion thresholds in human cerebral ischemia:historical perspective and therapeutic implications. Cerebrovasc Dis,2001, 11(suppl 1): 2-8.
[3]Kalogeris T, Baines CP, Krenz M, et al. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol,2012,298:229-317.
[4]Hermann DM, Zechariah A. Implications of vascular endothelial growth factor for postischemic neurovascular remodeling. J Cereb Blood Flow Metab,2009, 29(10):1620-1643.
[5]Chopp M, Li Y, Zhang J. Plasticity and remodeling of brain. J Neurol Sci, 2008,265(1-2):97-101.
[6]Han HS, Suk K. The function and integrity of the neurovascular unit rests upon the integration of thevascular and inflammatory cell systems. Curr Neurovasc Res,2005,2(5):409-423.
[7]Park JA, Choi KS, Kim SY, et al. Coordinated interaction of the vascular and nervous systems:fro mmolecule to cell-based approaches. Biochem Biophys Res Commun,2003,311 (2):247-253.
[8]Carmeliet P. Blood vessels and nerves:common signals, pathways and diseases. Nat Rev Genet,2003,4(9):710-720.
[9]Lok J, Gupta P, Guo S, et al. Cell-cell signaling in the neurovascular unit. Neurochem Res,2007,32(12):2032-2045.
[10]Hennigan A, O'Callaghan RM, Kelly AM. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans, 2007,35(Pt2):424-427.
[11]Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev,2005,57(2):173-185.
[12]del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab,2003,23(8):879-894.
[13]Chopp M, Li Y, Zhang J. Plasticity and remodeling of brain. J Neurol Sci, 2008,265(1-2):97-101.
[14]Ergul A, Alhusban A, Fagan SC. Angiogenesis:a harmonized target for recovery after stroke. Stroke,2012,43(8):2270-1174.
[15]Xiong Y, Mahmood A, Chopp M. Angiogenesis, neurogenesi s and brain recovery of function following injury. Curr Opin Investig Drugs,2010,11(3):298-308.
[16]Navaratna D, Guo S, Arai K, et al. Mechanisms and targets forangiogenic therapy after stroke. Cell Adh Migr,2009,3(2):216-223.
[17]Szpak GM, Lechowicz W, Lewandowska E, et al. Border zone neovascularization in cerebral ischemic infarct. Folia Neuropathol,1999,37(4):264-268.
[18]Hayashi T, Noshita N, Sugawara T, et al. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab,2003,23(2):166-180.
[19]Krupinski J, Issa R, Bujny T, et al. Aputative role for platelet-derived growth factor in angiogenesis and neuro protection after ischemic stroke in humans. Stroke,1997,28(3):564-573.
[20]Liu XS, Zhang ZG, Zhang RL, et al. Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells. J Cereb Blood Flow Metab,2007,27(3):564-574.
[21]Chen J, Cui X, Zacharek A, et al. Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke. J Cell Mol Mod,2009,13(7):1348-1357.
[22]Jiang WL, Zhang SP, Zhu HB, et al. Effect of 8-0-acetyl shanzhiside methylester increases angiogenesis and improves functional recoveryafter stroke. Basic Clin Pharmacol Toxicol,2011,108(1):21-27.
[23]Manoonkitiwongsa PS, Jackson-Friedman C, McMillan PJ, et al. Angiogenesis after stroke is correlated with increased numbers of macrophages:the clean-up hypothesis. J Cereb Blood Flow Metab,2001,21(10):1223-1231.
[24]Petraglia AL, Marky AH, Walker C, et al. Activated protein C is neuroprotective and mediates new blood vessel formation and neurogenesis after controlled cortical impact. Neurosurgery,2010,66(1):165-171; discussion 171-172.
[25]Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vasceular disorders. Blood,1998,91(10):3527-3561.
[26]Li N, Hu H, Lindqvist M, et al. Platelet-leukocyte cross talk in whole blood. Arterioscler Thromb Vasc Biol,2000,20(12):2702-2708.
[27]Esposito K, Marfella R, Ciotola M, et al. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome:a randomized trial. JAMA,2004,292(12):1440-1446.
[28]Baker RI, Eikelboom J, Lofthouse E, et al. Platelet glycoprotein Ibalpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood, 2001,98(1):36-40.
[29]Cherian P, Hankey GJ, Eikelboom JW, et al. Endothelial and platelet activation inacute ischemic stroke and its etiological subtypes. Stroke,2003, 34(9):2132-2137.
[30]Licata G, Tuttolomondo A, Di Raimondo D, et al. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost,2009,101(5):929-937.
[31]Hanson E, Jood K, Karlsson S, et al. Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke. J Thromb Haemost,2011, 9(2):275-281.
[32]畅慧君,张其相,卢红,等.急性脑梗死患者血清vWF的动态测定及临床研究.中国实用神经疾病杂志,2009,12(9)：1-3.
[33]Bongers TN, de Maat MP, van Goor ML, et al. High von Willebrand factor levels increase the risk of first ischemic stroke:influence of ADAMTS13, inflammation, and genetic variability. Stroke,2006,37(11):2672-2677.
[34]刘江,翟明,张蕾,等.昆明地区汉族人vWF基因多态性与急性脑梗死的相关性.中国神经精神疾病杂志,2011,37(9)：535-539.
[35]Carter AM, Catto AJ, Mansfield MW, et al. Predictive variables for mortality after acute ischemic stroke. Stroke,2007,38(6):1873-1880.
[36]Hanson E, Jood K, Nilsson S, et al. Association between genetic variation at the ADAMTS13 locus and ischemic stroke. J Thromb Haemost,2009, 7(12):2147-2148.
[37]Kleinschnitz C, De Meyer SF, Schwarz T, et al. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood,2009,113(15):3600-3603.
[38]Deng AJ, Jing DY. Sequential changes of HIF-1 a protein and mRNA in hypoxic bovine retinal microvessels endothelial cells. Int J Ophthalmol,2005, 5(2):225-228.
[39]Bergeron M, Yu AY, Solway KE, et al. Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eu J Neurosci, 1999, 11(12) :4159-4170.
[40]Demougeot C, Van Hoecke M, Bertrand N, et al. Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2' -dipyridyl in the rat photothrombotic ischemic stroke model. J Pharmacol Exp Ther, 2004, 311 (3): 1080-1087.
[41]Demougeot C,Van Hoecke M,Bertrand N, et al. Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2'-dipyridyl in the rat photothromboticischemicstroke model.JPharmacolExp Ther,2004, 311(3) :1080-1087.
[42]Mattson MP, Camandola S. NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest, 2001, 107(3):247-254.
[43]Aggarwal BB, Takada Y, Shishodia S, el al. Nuclear transcription factor NF-kappaB: role i n biology and medicine. Indian J Exp Biol, 2004, 42(4) :34 1-353.
[44]Schneider A, Martin-Vi1lalba A, WeihF, etal. NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat. Mod, 1999, 5(5) : 554-559.
[45]Ridder DA, Schwaninger M. NF-kappaB signaling in cerebral ischemia. Neuroscience, 2009, 158(3):995-1006.
[46]Brines M, Cerami A. Discovering crythropoictin's extra-hematopoietic functions: biology and clinical promise. Kidney Int, 2006, 70(2):246-250.
[47]Hicklin DJ, Ellis LM. Role of the vascular endothel ialgrowt h factor pathway in tumor growth and angiogenesis. J Clin Oncol, 2005, 23(5):1011-1027.
[48]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-inducedvascular endothelial growth factor expression precedes ncovascularization after cerebral ischemia. Am J Pathol, 2000, 156(3):965 - 976.
[49]Hickl in DJ, Ell is LM. Role of the vascular endothel ialgrowlh factor pathway in tumor growth and angiogenesis. J Clin Oncol, 2005, 23(5):1011-1027.
[50]Li Q, Stephenson D. Post ischemic administration of basic fibroblast growth factor improves sensorimotor function andreduces in Caret size following permanent focal cerebral ischemiain the rat. Exp Neurol, 2002, 177 (2):531-537.
[51]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-induccdvascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol,2000,156(3):965-976.
[52]王韧,侯立军.VEGF和内皮抑素对血管生成作用的研究进展.重庆医学,2011,40(25)：2582-2585.
[53]Presta M, Dell'Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev,2005,16(2):159-178.
[54]Wiedlocha A, S(?)rensen V. Signaling, internalization, and intracellular activity of fibroblast growth factor. Curr Top Microbiol Immunol,2004, 286:45-79.
[55]Edwards AK, van den Heuvel MJ, Wessels JM, et al. Expression of angiogenic basic fibroblast growth factor, platelet derived growth factor, thrombospondin-1 and their receptors at the porcine maternal-fetal interface. Reprod Biol Endocrinol,2011,9:5.
[56]Li WL, Yamada Y, Ueno M, et al. Platelet-derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis. J Biochem,2006,140(2):267-273.
[57]Facchiano A, De Marchis F, Turchetti E, et al. The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor. J Cell Sci,2000,113(Pt 16):2855-2863.
[58]De Marchis F, Ribatti D, Giampietri C, et al. Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its alpha receptor. Blood,2002,99(6):2045-2053.
[59]Tengood JE, Ridenour R, Brodsky R, et al. Sequential delivery of basic fibroblast growth factor and platelet-derived growth factor for angiogenesis. TissueEng Part A,2011,17(9-10):1181-1189.
[60]高娜,吴涛.TGF-β在卵巢癌中作用的研究进展.大连医科大学学报,2012,34(4)：409-412.
[61]Bertolino P, Deckers M, Lebrin F, et al. Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest,2005,128(6 Suppl):585S-590S.
[62]Goumans MJ, Lebrin F, Valdimarsdottir G. Controlling the angiogenic switch: abalance between two distinct TGF-b receptor signaling pathways. Trends Cardiovasc Med,2003,13(7):301-307.
[63]Bertolino P, Deckers M, Lebrin F, et al. Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest, 2005, 128(6 Suppl):585S-590S.
[64]Holderfield MT, Hughes CC. Crosstalk between vascular endothelial growth factor, notch, and transforming growth factor-beta in vascular morphogenesis. Circ Res, 2008, 102(6) :637-652.
[65]van Meeteren LA, Goumans MJ, ten Di jke P. TGF-β receptor signaling pathways in angiogenesis; emerging targets for anti-angiogenesis therapy. Curr Pharm Biotechnol, 2011, 12(12):2108-2120.
[66]Xin X, Yang S, Ingle G, et al. Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Am J Pathol, 2001, 158(3) : 1111-1120.
[67]Sengupta S, Sellers LA, Gherardi E, etal. Nitric oxide modulates hepatocyte growth factor/scatter factor-induced angiogenesis. Angiogenesis, 2004, 7(4) : 285-294.
[68]Kaga T, Kawano H, Sakaguchi M, et al. Hepatocyle growth factor stimulated angiogenesis without inflammation: Differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor. Vascul Pharmacol, 2012, 57(1):3-9.
[69]Freret T,Valable S,Chazalviel L, et al. Delayed administration of deferoxamine reduces brain damage and promotes functional recovery after transient focal cerebralischemiainthe rat.Eur J Neurosci,2006, 23(7) : 1757-1765.
[70]Iwai M, Cao G, Yin W, et al. Ery thropoiet i n promotes neuronal replacement through revascularizalion and neurogenesis after neonatal hypoxia/ischemia in rats. Stroke, 2007, 38(10) :2795-2803.
[71]Semen/a GL, Shimoda LA, Prabhakar NR. Regulat ion of gene expression by HIF-1. Novartis Found Symp, 2006, 272:2-8.
[72]May D, Itin A, Gal 0, Kalinski H, et al. Erol-L alpha plays a key role in a MIF01-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer. Oncogene, 2005, 24(6): 1011-1020.
[73]Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci, 2004, 5(6): 437-448.
[74]Semenza GL. Angiogenesis in ischemic and neoplastic disorders. Ann Rev Med, 2003,54:17-28.
[75]Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med,2002,8(8):495-505.
[76]Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol,2000,156(3):965-976.
[77]Sasabe E, Tatemoto Y, Li D, et al. Mechanism of HIF-lalpha-dependent suppression of hypoxia-induced apoptosis insquamous cell carcinoma cells. Cancer Sci,2005,96(7):394-402.
[78]Li J, Zhang X, Se jas DP, et al. Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. J Biol Chem,2004,279(40):41275-41279.
[79]Carmeliet P, Dor Y, Herbert JM, et al. Role of HIF-lalpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature,1998, 394(6692):485-490.
[80]Ribatti D, Vacca A, Roccaro AM, et al. Erythropoietin as an angiogenic factor. Eur J Clin Invest,2003,33(10):891-896.
[81]Li F, Chong ZZ, Maiese K. Erythropoietin on a tightrope:balancing neuronal and vascular protection between intrinsic and extrinsic pathways. Neurosignals, 2004,13(6):265-289.
[82]Bernaudin M, Marti HH, Roussel S, et al. A potential rolefor erythropoietin in focal permanent cerebral ischemia in mice.J Cereb Blood Flow Metab, 19(6)643-651.
[83]Holstein JH, Orth M, Scheuer C, et al. Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in a femoral segmental defect model in mice. Bone,2011,49(5):1037-1045.
[84]Beck H, Voswinckel R, Wagner S, et al. Participation of bone marrow-derived cells in long-term repair processes after experimental stroke. J Cereb Blood Flow Metab,2003,23(6):709-717.
[85]Sobrino T, Hurtado 0, Moro MA, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke,2007,38(10):2759-1764.
[86]Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke,2008, 39(1):69-74.
[87]Fan Y, Shen F, Frenzel T, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol,2010,67(4):488-497.
[88]王宇,马淑兰,崔建美,等.针刺抗哮喘大鼠血清差异组份的色谱分析.上海针灸杂志,2006,25(8)：41-43.
[89]Wang Yu, Yang Yong qing, MA Shu Ian, et al. SDS-PAGE analysis of components in serum with anti-asthma activity derived from rats treated by acupuncture. J Acupuncture Tuina Sci,2009,7:8-12.
[90]陈云飞,杨文佳,马晓芃,等.不同时段艾灸血清中内生性蛋白组分双向电泳的实验研究.上海中医药大学学报,2007,21(2)：57-60.
[91]王素娥,彭争荣,钟广伟,等.针刺血清对脑源性神经干细胞分化的影响.中国康复医学杂志,2007,22(5)：459-460.
[92]Dunning MD, Lakatos A, Loizou L, et al. Superparamagnetic i ronoxide-labeled schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS. Neurosci,2004,24(44):9799-9810.
[93]秦逸人,赵英侠.针灸治疗骨质疏松的临床与实验研究新进展.中医杂志,2005,46(增刊)：306.
[94]赵英侠,王静,秦逸人,等.针刺血清对体外培养破骨细胞数量的影响.中国针灸,2007,27(7)：521-524.
[95]赵英侠,王静,秦逸人,等.经针刺去除卵巢大鼠血清对体外培养破骨细胞骨吸收功能的影响.中国康复医学杂志,2008,23(5)：420-422.
[96]宋秀娟,陈晞,汪洋,等.兔胸段脊髓损伤后不同组穴的针刺血清对体外脊髓神经元生长的影响.宁夏医学杂志,2009,31(2)：133-135.
[97]罗明富,李翠红,张金铃,等.针刺血清降低大鼠培养心肌细胞内Ca2+含量的研究.中国针灸,2006,26(5)：367-369.
[98]罗明富,李翠红,张金铃,等.针刺血清对培养心肌细胞线粒体功能影响的观察.针刺研究,2005,30(3)：153-154.
[99]李瑞午,张静龄,郭莹,等.针刺血清对体外培养神经细胞内钙离子浓度的影响.中西医结合学报,2004,2(6)：453-455.
[100]邓元江,易受乡,严洁,等.促阳明经穴针刺血清对家兔离体胃窦平滑肌细胞舒缩活动的影响.中医杂志,2005,46(4)：264-266.
[101]邓元江,易受乡,严洁,等.足阳明经穴针刺血清对家兔离体胃窦平滑肌细胞内 钙离子浓度影响的实验研究.新中医,2005,37(10)：91-93.
[102]邰浩清,周春祥,姜文芳.针刺动物血清对内耳干细胞分化影响的实验研究.南京中医药大学学报,2009,25(5)：367-369.
[103].Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science,1997,275 (5302):964-977.
[104]Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological andpathological neovascularization. Circ Res,1999,85(3):221-228.
[105]Risau W, Flamme I. Vaseulogenesis. Ann Rev Cell Dev Biol,1995,11 (9):79-91 106 Folkman J, Shing Y. Angiogenesis. Boil Chem,1992,267(16):10931-10934.
[107]Suda T, Takakura N, Oike Y. Hematopoiesis and angiogenesis. Int J Hematol, 2000,71(2):99-107.
[108]Urbich C, Dimmeler S. Endothelial progenitor cells:characterization and role in vascularbiology. Circ Res,2004,95(4):343-353.
[109]Asahara T, Kawamoto A, Masuda H. Concise review:Circulating endothelial progenitor cells for vascular medicine. Stem Cells,2011,29(11):1650-1655.
[110]Lin Y, Weisdorf D, Solovey A, et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest,2000,105(1):71-77.
[111]Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood,1998,92(2):362-367.
[112]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24(2):288-293.
[113]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[114]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24(2):288-293.
[115]Sieveking DP, Buckle A, Celermajer DS, et al. Strikingly different angiogenic properties of endothelial progenitor cell subpopulations:insights from a novel human angiogenesis assay. J Am Coll Cardiol,2008,51(6):660-668.
[116]Aicher A, Rentsch M, Sasaki K, et al. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res, 2007, 100(4):581-589.
[117]Wojakowski W, Kucia M, Kazmierski M, et al. Circulating progenitorcells in stable coronary heart disease and acute coronary syndromes: Relevant reparatory mechanism?. Heart, 2008, 94 (1):27-33.
[118]Losordo DW, Kishore R. A big promise from the very small identification of circulating embryonic stem-like pluripotent cells in patients with acute myocardial infarction.J Am Coll Cardiol, 2009, 53(1):10-12.
[119]Umemura T, HigashiY. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci, 2008, 108(1):1-6.
[120]Ding H, Triggle CR. Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium. Vasc Heal th Risk Manag, 2005, 1(1):55-71.
[121]Caballero S, Sengupta N, Afzal A, et al. Ischcmic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes, 2007, 56(4) : 960-967.
[122]Shi Q, Raf i i S, Wu MH, et al. Evidence for eirculat ing bonemarrow-derived endolhelial cells. Blood, 1998, 92(2):362-367.
[ 123]Garcia-Barros M, Paris P, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis.Science,2003, 300(5622):1155-1159.
[124]Casamassimi A, Balestrieri ML, Fiorito C, et al. Comparison between total endothelial progenitor cell isolation versus enriched Cd133+ culture. J Biochem, 2007, 141(4) : 503-511.
[125]Nakahata T, Ogawa M. Hemopoietic colony-forming cells in umbilical cord blood wi th extensive capabi 1 i ty to generate mono- and mul tipotent ial hemopoietic progenitors. J Clin Invest, 1982, 70(6):1324-1328.
[ 126]Mayani II, Lansdorp PM. Thy—1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human urnbilical cord blood. Blood, 1994, 83(9) :2410-2417.
[127]Murohara T, Ikeda II, Duan J, et al. Transplanted cord blood-derived endothelial precursor colls augment postnalal neovascularization. J Clin Invest, 2000, 105(11): 1527-1536.
[128]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[129]Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue:implications for cell-based therapies. Tissue Eng,2001,7(2):211-228.
[130]Planat-Benard V, Silvestre JS, Cousin B, et al. Plasticity of human adipose lineage cells toward endothelial cells:physiological and therapeutic perspectives. Circulation,2004,109(5):656-663.
[131]Miranville A, Heeschen C, Sengenes C, et al. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation, 2004,110(3):349-55.
[132]周秀娟.人外周血、脐血、脂肪组织中内皮祖细胞生物特性比较研究.中国动脉硬化杂志,2008,19(8)：675-679.
[133]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003,93(2):e17-24.
[134]Tamaki T, Akatsuka A, Ando K, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol, 2002,157(4):571-577.
[135]Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell,2003,114(6):763-776.
[136]Cherqui S, Kurian SM, Schussler O, et al. Isolation and angiogenesis by endothelial progenitors in the fetal liver. Stem Cells,2006,24(1):44-54.
[137]Hirschi KK, Goodell MA. llematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Ther,2002,9(10):648-652.
[138]Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood,2000, 95(10):3106-3112.
[139]Harraz M, Jiao C, Hanion HD, et al. CD34-blood-derived human endothelial cells progenitors. Stem Cells,2001,19(4):304-312.
[140]Shintani S, Murohara T, Ikeda H, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation, 2001,103(6):897-903.
[141]Li L, Xie T. Stem cell niche:structure and function. Annu Rev Cell Dev Biol,2005,21:605-631.
[142]Yin T, LiL The stem cell niches in bone. J Clin Invest, 2006, 116(5): 1195-1201.
[143]Shepherd RM, Capoccia BJ, Devine SM, et al. Angiogenic cells can be rapidly mobilized and efficiently harvestedfrom the blood following treatment with amd3100. Blood, 2006, 108:3662-3667.
[144]Ramirez P, Rettig MP, Uy GL, et al. BI05192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem andprogenitor cells. Blood, 2009, 114:1340- 1343.
[145]Walter DH, Rochwalsky U, Reinhold J, et al. Sphingosine-1-phosphate stimulates the functional capacity ofprogenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arterioscler Thromb Vasc Biol, 2007, 27(2):275-282.
[146]Sumi M, Sata M, Miura S, et al. Reconstituted high-density lipoprotein stimulates differentiation ofendothelial progenitor cells and enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol, 2007, 27(4) 813-818.
[147 ]Murayama T, Topper OM, Silver M, et al. Determination of bone marrow-derived endothelialprogenitor cellsignificancein angiogenic growthfactor-inducedneovascularizationinvivo.ExpHomatol,2002, 30(8) : 967-972.
[148]Hiasa K, Ishibashi M,Ohtani K, et al. Gene transfer of stromal cell-derivedfactor-lalpha enhances ischemia vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation, 2004, 109 (20) :2454-2461.
[149]Zeng L, Xiao Q,Margariti A, et al. IIDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. J Cell Biol, 2006, 174(7):1059-1069.
[150]Jie KE, Goossens MH, van Oostrom 0, et al. Circulating endothelial progenitor cell levels are higher during childhood than in adult life. Atherosclerosis, 2009, 202(2):345-347.
[151]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity ofcirculating endothelial progenitor cells inversely correlate with risk factors forcoronary artery disease. Circ Res,2001,89(1):El-7.
[152]Heiss C, Keymel S, Niesler U, et al. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol,2005, 45(9):1441-1448.
[153]Kushner EJ, Van Guilder GP, Maceneaney OJ, et al. Aging and endothelial progenitor cell telomere length in healthy men. Clin Chem Lab Med,2009, 47(1):47-50.
[154]He T, Joyner MJ, Katusic ZS. Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells. Microvasc Res, 2009,78(3):447-452.
[155]Thum T, Hoeber S, Froese S, et al. Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulinlike growth-factor-1. Circ Res,2007,100(3):434-443.
[156]Hoetzer GL, Van Guilder GP, Irmiger HM, et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. J Appl Physiol,2007,102(3):847-852.
[157]Chang EI, Loh SA, Ceradini DJ, et al. Age decreases endothelial progenitor cellrecruitment through decreases in hypoxia-inducible factor lalpha stabilization during ischemia. Circulation,2007,116(24):2818-2829.
[158]Hoetzer GL, MacEneaney OJ, Irmiger HM, et al. Gender differences in circulatingendothelial progenitor cell colony-forming capacity and migratory activity inmiddle-aged adults. Am J Cardiol,2007,99(1):46-48.
[159]Fadini GP, de Kreutzenberg S, Albiero M, et al. Gender differences in endothelial progenitor cells and cardiovascular risk profile:the role of female estrogens. Arterioscler Thromb Vasc Biol,2008,28(5):997-1004.
[160]Stauffer BL, Maceneaney OJ, Kushner EJ, et al. Gender and endothelial progenitor cell number in middle-aged adults. Artery Res,2008,2(4):156-160.
[161]Fadini GP, de Kreutzenberg S, Albiero M, et al. Gender differences in endothelial progenitor cells and cardiovascular risk profile:the role of female estrogens. Arterioscler Thromb Vasc Biol,2008,28(5):997-1004.
[162]Imanishi T, Hano T, Nishio I. Estrogen reduces angiotensin Ⅱ-induced acceleration of senescence in endothelial progenitor cells. Hypertens Res,2005, 28(3):263-271.
[163]Bogdanski P, Miller-Kasprzak E, Pupek-Musialik D, et al. Evaluation of Endothelial progenitor cells in patients with hypertension:Pp.6.248. J Hypertens,2010,28:pe124.
[164]Georgescu A, Alexandru N, Andrei E, et al. Circulating microparticles and endothelial progenitor cells in atherosclerosis:pharmacological effects of irbesartan. J Thromb Haemost,2012,10(4):680-691.
[165]Dernbach E, Randriamboavonjy V, Fleming I, et al. Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors. Basic Res Cardiol,2008,103(6):572-581.
[166]Alexandru N, Popov D, Dragan E, et al. Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia. PLoS One,2013,8(1):e52058.
[167]Min TQ, Zhu CJ, Xiang WX, et al. Improvement in endothelial progenitor cells from peripheral blood by ramipril therapy in patients with stable coronary artery disease. Cardiovasc Drugs Ther,2004,18(3):203-209.
[168]Yu Y, Fukuda N, Yao EH, et al. Effects of an ARB on endothelial progenitor cell function and cardiovaseular oxidation in hypertension. Am J Hypertens,2008, 21(1):72-77.
[169]Menegazzo L, Albiero M, Avogaro A, et al. Endothelial progenitor cells in diabetes mellitus. Biofactors,2012,38(3):194-202.
[170]Topper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells fromtype Ⅱ diabetics exhibit impaired proliferation, adhesion, and incorporation intovascular structures. Circulation,2002,106(22):2781-2786.
[171]Voo S, Dunaeva M, Eggermann J, et al. Diabetes mellitus impairs CD133+ progenitor cell function after myocardial infarction. J Intern Mod,2009, 265(2):238-249.
[172]Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction:a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes,2004,53(1):195-199.
[173]Hamed S, Brenner B, Aharon A, et al. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus. Cardiovasc Diabetol,2009,8:56.
[174]Kuki S, Imanishi T, Kobayashi K, et al. Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J,2006,70(8):1076-1081.
[175]Rosso A, Balsamo A, Gambino R, et al. p53 Mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes. J Biol Chem,2006, 281(7):4339-4347.
[176]Zhang W, Wang X, Jin H, et al. Effects of high glucose plus high insulin on proliferation and apoptosis of mouse endothelial progenitor cells. Inflamm Res,2008,57(12):571-576.
[177]Jung C, Rafnsson A, Shemyakin A, et al. Different subpopulations of endothelial progenitor cells and circulating apoptotic progenitor cells in patients with vascular disease and diabetes. Int J Cardiol,2010, 143(3):368-372.
[178]Chen YH, Lin SJ, Lin FY, et al. High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes,2007,56(6):1559-1568.
[179]Bhatwadekar AD, Glenn JV, Li G, et al. Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells:implications for vasodegeneration in diabetic retinopathy. Invest Ophthalmol Vis Sci,2008, 49(3):1232-1241.
[180]Urbich C, Dernbach E, Rossig L, et al. High glucose reduces cathepsin L act ivi ty and impairs invasion of circulating progenitor cells. J Mol Cell Cardiol, 2008,45(3):429-436.
[181]Liang C, Ren Y, Tan H, et al. Rosigl i tazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products. Br J Pharmacol,2009,158(8):1865-1873.
[182]Chen Q, Dong L, Wang L, et al. Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2. Biochem Biophys Res Commun,2009,381(2):192-197.
[183]Shen C, Li Q, Zhang YC, et al. Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways. Biomed Pharmacother,2010,64(1):35-43.
[184]Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors forcoronary artery disease. Circ Res,2001,89(1):E1-7.
[185]Ma FX, Zhou B, Chen Z, et al. Oxidized low density lipoprotein impairs endothelial progeni tor cells by regulation of endothelial nitrie oxide synthase. J Lipid Res, 2006, 47(6) : 1227-1237.
[186]Petoumenos V, Nickenig G, Werner N. High density lipoprotein exerts vasculoprotection via endothelial progenitor cells. J Cell Mol Med, 2009, 13(11-12):4623-4635.
[187]Noor R, Shuaib U, Wang CX, et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis, 2007, 192(1):92-99.
[188]Sobrino T, Blanco M, Perez-Mato M, et al. Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase. Eur J Neurol, 2012, 19(12):1539-1546.
[189]MacEneaney 0J, Kushner EJ, Van Guilder GP, et al. Endothelial progenitor cell number and colony-forming capacity in overweight and obese adults. Int J Obes(Lond), 2009, 33(2):219-225.
[190]Maceneaney OJ, Kushner EJ, Westby CM, et al. Endothelial progenitor cell function, apoptosis, and telomere length in overweight/obese humans. Obesity(Silvor Spring), 2010, 18(9):1677-1682.
[191]Westerweel PE, Visseren FL, Hajer GR, et al. Endothelial progenitor cell levels in obese men with the metabolic syndrome and the effect of simvastat in monotherapy vs. simvastatin/ezetimibe combination therapy. Eur Heart J, 2008, 29(22) : 2808-2817.
[192]Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 2004, 364(9438):937-952.
[193]Kondo T, Hayashi M, Takeshita K, et al. Smoking cessation rapidly increasescirculating progenitor cells in peripheral blood in chronic smokers. Arteriosc lerThromb Vasc Biol, 2004, 24(8): 1442-1447.
[194]Michaud SE, Dussault S, Haddad P, et al. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis, 2006, 187(2):423-432.
[195]van Grevenynghe J, Monteiro P, Gilot D, et al. Human endothelial progenitors constitute targets for environmental atherogenic polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun, 2006, 341 (3) :763-769.
[196]Fujioka D, Kawabata K, Saito Y, et al. Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression ininfarcted heart. Am J Physiol Heart Circ Physiol,2006, 290(6):H2409-2416.
[197]Sugimoto A, Masuda H, Eguchi M, et al. Nicotineenlivenment of blood flow recovery following endothelial progenitor cell transplantation into ischemic hindlimb. Stem Cells Dev,2007,16:649-656.
[198]Heiss C, Amabile N, Lee AC, et al. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function:sustained vascular injury and blunted nitric oxide production. J Am Coll Cardiol,2008, 51 (18):1760-1771.
[199]Masuda H, Kalka C, Takahashi T, et al. Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res,2007,101 (6):598-606.
[200]Bauer SM, Goldstein LJ, Bauer RJ, et al. The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia. J Vase Surg,2006,43(1):134-141.
[201]Iwakura A, Shastry S, Luedemann C, et al. Estradiol enhances recovery after myocardial infarction by augmenting incorporation of bone marrow-derived endothelial progenitor cells into sites of ischemia-induced neovascularization via endothelial nitric oxide synthase-mediated activation of matrix metalloproteinase-9. Circulation,2006,113(12):1605-1614.
[202]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30(8):967-972.
[203]Masuda 11, Kalka C, Takahashi T, et al. Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. Circ Res,2007,101 (6):598-606.
[204]Ii M, Nishimura H, Iwakura A, et al. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via "imported" nitric oxide synthase activity. Circulation, 2005,111(9):1114-1120.
[205]Miyamoto Y, Suyama T, Yashita T, et al. Bone marrow subpopulations contain distinct types of endothelial progenitor cells and angiogenic cytokine-producing cells. J Mol Cell Cardiol, 2007, 43(5):627-635.
[206]Jujo K,li M,Losordo DW.Endothelial progenitor cells in neovascularization of infarcted myocardium.J Mol Cell Cardiol,2008, 45(4) : 530-544.
[207]Kawamoto A,Tkebuchava T, Yamaguchi J, et al.Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation, 2003, 107(3):461-468.
[208]Kalka C, Masuda H,Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA, 2000, 97(7):3422-3427.
[209]Hess DC, Hill WD, Martin-Studdard A, et al. Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke. Stroke, 2002, 33(5) : 1362-1368.
[210]Wu X, Rabkin-Aikawa E, Guleserian KJ, et al. Tissue engineered microvossels on three-dimensional biodegradable scaffolds using human endothel ial progenitor cells. Am J Physial Heart Circ Physiol, 2004, 287(2):480-487.
[211]Shirota T, Yasu i H, Shimokawa H, et al. Fabrication of endothelial progenitor coll (EPC) -seeded intravascular stent devices and invitro endothelialization on hybrid vascular tissue. Biomaterials, 2003, 24(13) : 2295-2302.
[212]Taguchi A,Matsuyama T,Moriwaki H, et. al. Circulating CD34-positive cells provide an index of cerebrovascular function. Circulation, 2004, 109(24):2972-2975.
[213]Ghani U, Shuaib A, Salam A, et al. Endothelial progenitor cells during cerebrovascular disease. Stroke, 2005, 36(1):151-153.
[214]Fadini GP, Coracina A, Baesso I, et al. Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke, 2006, 37(9):2277-2282.
[215]Chu K,Jung KH, Lee ST, et al. Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke. Stroke, 2008, 39(5) : 1441-1447.
[216]Yip HK, Chang LT, Chang WN, et al. Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke, 2008, 39(1):69-74.
[217]Sobrino T, Hurtado 0, Moro MA, et al. The increase of circulating endothelial progenitor cells after acute ischemic stroke is associated with good outcome. Stroke,2007,38(10):2759-2764.
[218]Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest, 2004,114(3):330-338.
[219]Morgan R, Kreipke CW, Roberts G, et al. Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis. Neurol Res,2007,29(4):375-381.
[220]Brea D, Rodriguez-Gonzalez R, Sobrino T, et al. Proteomic analysis shows differential protein expression in endothelial progenitor cells between healthy subjects and ischemic stroke patients. Neurol Res,2011,33(10):1057-1063.
[221]Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem cell reviews,2011,7(1):208-220.
[222]Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics--2008 update:a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation,2008,117(4): e25-146.
[223]Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update:a report from the American Heart Association. Circulation,2013,127(1):e6-e245.
[224]American Heart Association. Heart disease and stroke statistics--2005 Update. Dallas, Texas:American Heart Association,2005.
[225]Roger VL, Go AS, Lloyd-Jones DM, et al. Heart diseas and stroke statistics-2012 update:a report from the American Heart Association. Circulation,2012, 125(1):e2-e220.
[226]Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol,2002,30(8):967-972.
[227]刘轲,李建生,周友龙,等.脑脉通对老龄大鼠脑缺血/再灌注微血管生成及bFGF. TGF表达的影响.中华中医药杂志(原中国医药学报),2010,25(8)：1188-1192.
[228]Belayev L, Endres M, Prinz V, et al. Focal cerebral ischemia in the mouse and rat using the intraluminal suture-filament model. Neuromethods,2010, 47:29-40
[229]Aspey BS, Cohen S, Patel Y, et al. Middle cerebral artery occlusion in the rat:consistent protocol for a model of stroke. Neuropathol Appl Neurobiol, 1998,24(6):487-497.
[230]Oliff HS, Coyle P, Weber E. Rat strain and vendor differences in collateral anastomoses. J Cereb Blood Flow Metab,1997,17:571-578.
[231]Bardutzky J, Shen Q, Henninger N, et al. Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging. Stroke, 2005,36(9):2000-2005.
[232]Encarnacion A, Horie N, Keren-Gill H, et al. Long-term behavioral assessment of function in an experimental model for ischemic stroke.2011, 196(2):247-257.
[233]龚彪,李长清,黄剑.SD大鼠线栓法局灶性脑缺血/再灌注模型的改进.重庆医学,2006,35(4)：313-315.
[234]Alkayed NJ, Harukuni I, Kimes AS, et al. Gender-linked brain injury in experimental stroke. Stroke,1998,29(1):159-165.
[235]Saltiki K, Alevizaki M. Coronary heart disease in postmenopausal women; therole of endogenous estrogens and their receptors. Hormones(Athens),2007, 6(1):9-24.
[236]Plamondon H, Morin A, Charron C. Chronic 17beta-estradiol pretreatment and ischemia-induced hippocampal degeneration and memory impairments:a 6-month survival study. Horm Behav,2006,50(3):361-369.
[237]Wang LC, Futrell N, Wang DZ, et al. A reproducible model of middle cerebral infarcts, compatible with long-term survival, in aged rats. Stroke,1995, 26(11):2087-2090.
[238]文灿,朱星红.大鼠大脑中动脉的衰老性变化.解剖学杂志,2004,27(5)：528
[239]谢宁,段新芬,牛英才.线栓法制备大鼠大脑中动脉脑缺血动物模型影响因素探析.中医药管理杂志,2006,14(12)：51.
[240]赵帅,樊小农,孟智宏,等.线栓法制备大鼠中动脉缺血闭塞模型研究进展.江西中医药,2012,43(351)：77-80
[241]许天新,蔡德雷,郑云燕,等.4-8周龄SD大鼠体重和主要脏器正常参考值.浙江预防医学,2006,18(8)：73-75
[242]Cruz-Flores S, Berge E, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev,2012, 1:CD003435.
[243]吴忧,贾建平.脑缺血动物模型的制备及影响因素.中国脑血管病杂志,2007,4(1)： 42-44
[244]Koizumi J, Yoshida Y, Nazawa T, et al. Experimental studies of ischemia brain edema,1:A new experimental model of cerebral embolism infarcts in the ischemia area. Stroke,1986, (8):1-8.
[245]Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke,1989,20(1):84-91
[246]Wiedlocha A, S(?)rensen V. Signaling, internalization, and intracellular activity of fibroblast growth factor.Curr Top Microbiol Immunol,2004, 286:45-79.
[247]FolkmanJ, KlagsbrumM. Angiogenic factors. Science,1987,235:442-447
[248]Damico FM. Angiogenesis and retinal diseases. Arq BrasOftlmol,2007, 70(3):547-553
[249]Bottcher RT, Niehrs C. Fibroblast growth factor signaling during early vertebrate development. Endocr Rev,2005,26(1):63-77.
[250]Stavri GT, Zachary IC, Baskerville PA, et al. Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle colls. Synergistic interaction wi th hypoxia. Circulation, 1995,92(1):11-14
[251]Asahara T, Bauters C, Zheng LP, et al. Synergistic effect of vascular endothelial growth factorand basic fibroblast growth factor on angiogenesis in vivo. Circulation,1995,92(9 Suppl):11365-371.
[252]Koivisto H, Hyvarinen M, Stromberg AM, et al. Cultures of human embryonic stem cells:serum replacement medium or serum-containing media and the effect of basic fibroblast growth factor. Reprod Biomed Online,2004,9(3):330-337
[253]Sun XT, Ding YT, Yan XG, et al. Angiogenic synergistic effect of basic fibroblast growth factor and vascular endothelialgrowthfactorin an in vitro quantitative microcarrier-based three-dimensional fibrin angiogenesis system. World J Gastroenterol,2004,10(17):2524-2528.
[254]Akasaka Y, Ono I, Yamashita T, et al. Basic fibroblast growth factor promotes apoptosis and suppresses granulation tissue formation in acute incisional wounds. J Pathol,2004,203(2):710-720.
[255]Doi K, Ikeda T, Marui A, et al. Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischaemia. Heart Vessels,2007,22:104-108.
[256]Cao Y, Cao R, Hedlund EM. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med (Berl),2008, 86(7):785-789.
[257]Mavria G, Vercoulen Y, Yeo M, et al. ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell,2006,9(1):33-44.
[258]Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci,2001,22(4):201-207.
[259]Maffucci T, Raimondi C, Abu-Hayyeh S, et al. A phosphoinositide 3-kinase/phospholipase Cgammal pathway regulates fibroblast growth factor-induced capillary tube formation. PLoS One,2009,4(12):e8285.
[260]Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res,2007,100(6):782-794.
[261]Li S, Huang NF, Hsu S. Mechanotransduction in endothelial cellmigration. J Cell Biochem,2005,96(6):1110-1126.
[262]徐彬,武晓英,林桂先,等.bFGF基因转染对血管内皮细胞迁移的影响及机制.山东医药,2010,(11)：21-24
[263]Shi C, Lu J, Wu W, et al. Endothelial cell-specific molecule2 (ECSM2) localizes to cell-cell junctions and modulates bFGF-directed cell migration via the ERK-FAKpathway. PLoS One,2011,6(6):e21482.
[264]Rafat N, Beck Gch, Pean-Tapia PG, et al. Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease. Stroke,2009, 40(2):432-438.
[265]Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat.1995,36(2):169-180.
[266]Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol,1995,147(1):9-19.
[267]Mahzouni P, Mohammadizadeh F, Mougouei K, et al. Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor Ⅷ-related antigen" (von Willebrand factor) expression in tumor microvessels. Indian J Pathol Microbiol,2010, 53(4):605-610.
[268]Horak ER, Leek R, Klenk N, et al. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet,1992,340(8828):1120-1124.
[269]da Silva BB, Lopes-Costa PV, dos Santos AR, et al. Comparison of three vascular endothelial markers in the evaluation of microvessel density in breast cancer. Eur J Gynaecol Oncol,2009,30(3):285-288.
[270]Ahrens I, Domeij H, Topcic D, et al. Successful in vitro expansion an differentiation of cord blood derived CD34+ cells into early endothelial progenitor cells reveals highly differential gene expression. PLoS One,2011, 6(8):e23210.
[271]Thill M, Strunnikova NV, Berna MJ, et al. Late outgrowth endothelial progenitor cells in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci,2008,49(6):2696-2708.
[272]UmemuraT, HigashiY. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci,2008,108(1):16.
[273]Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science,2003, 300(5622):1155-1159.
[274]Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood,2004,104(9):2752-2760.
[275]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003,93(2):e17-24.
[276]Cherqui S, Kurian SM, Schussler 0, et al. Isolation and angiogenesis by endothelial progenitors in the fetal liver. Stem Cells,2006,24(1):44-54.
[277]Casamassimi A, Balestrieri ML, Fiorito C, et al. Comparison between total endothelial progenitor cell isolation versus enriched Cd133+ culture. J Biochem, 2007,141(4):503-511.
[278]Kahler CM, Wechselberger J, Hilbe W, et al. Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury. Respir Res,2007,8:50.
[279]Chen YH, Lin SJ, Lin FY, et al. High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes,2007,56(6):1559-1568.
[280]Hur J, Yoon CH, Kim HS, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol,2004,24:288-293.
[281]Peichev M, Naiyer AJ, PereiraD, et al. Expression of VEGFR-2 and AC133 by circulating human CD34 (+) cells identifies a population of functional endothelial precursors. Blood,2000,95(3):952-958.
[282]Yoder MC. Defining human endothelial progenitor cells. J Thromb Haemost. 2009,7 Suppl 1:49-52.
[283]Dimmeler S. Regulation of bone marrow-derived vascular progenitor cell mobilization and maintenance. Arterioscler Thromb Vase Biol.2010,30(6): 1088-1093.
[284]Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood,1997,90(12):5002-5012.
[285]Leone AM, Valgimigli M, Giannico MB, et al. From bone marrow to the arterial wall:the ongoing tale of endothelial progenitor cells. Eur Heart,2009, 30(8):890-899.
[286]Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol,2004,287(3):C572-579.
[287]Mizrak D, Brittan M, Alison M. CD133:molecule of the moment. J Pathol. 2008,214(1):3-9.
[288]Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene,2000, 19(49):5598-5605.
[289]Timmermans F, Plum J, Yoder MC, et al. Endothelial progenitor cells: identity defined?. J Cell Mol Med,2009,13(1):87-102.
[290]Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood, 2007,109(5):1801-1809.
[291]Hirschi KK, Ingram DA, Yoder MC, et al. Assessing identity, phenotype, and fate of endothelial progenitorcells. Arterioscler Thromb Vasc Biol,2008, 28(9):1584-1595.
[292]Yoder MC. Defining human endothelial progenitor cells. J Thromb Haemost, 2009, Suppl 1:49-52.
[293]Johansson CB, Momma S, Clarke DL, et al. Identification of a neural stem cell in the adult mammalian central nervoussystem. Cell,1999,96(1):25-34.
[294]Mothe AJ, Tator CH. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neurosci ence,2005,131(1):177-187.
[295]Meng QY, Li XQ, Yu XB, et al. Transplantation of VEGF165-gene-transfected endothelial progenitor cells in the treatment of chronic venous thrombosis in rats. Chin Med J(Engl),2010,123(4):471-477.
[296]Voyta JC, Via DP, Butterfield CE, etal. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol,1984,99(6):2034-2040.
[297]方立建.人脐带血内皮祖细胞的培养与鉴定.长春：吉林大学,2008.
[298]Yang C, Zhang ZH, Li ZJ, et al. Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation. Thromb Haemost,2004,91 (6):1202-1212.
[299]Holthofer H, Virtanen I, Kariniemi AL, etal. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest,1982, 47(1):60-66.
[300]Suzuki K, Sakata N, Kitani A, et al. Characterization of human monocytic cell line, U937, in taking up acetylated low-density lipoprotein and cholesteryl ester accumulation. A flow cytometric and HPLC study. Biochim Biophys Acta,1990, 1042(2):210-216.
[301]Urbich C, Heeschen C, Aicher A, et al. Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells. Circulation,2003,108(20):2511-2516.
[302]Rohde E, Malischnik C, Thaler D, et al. Blood monocytes mimic endothelial progenitor cells. Stem Cells,2006,24(2):357-367.
[303]Graziano M, St-Pierre Y, Potworowski EF. UEA-I-binding to thymic medullary epithelial cells selectively reduces numbers of cortical TCRalphabeta+ thymocytes in FTOCs. Immunol Lett,2001,77(3):143-150.
[304]Liu SM, Li CY. Immunohistochemical study of Ulex europaeus agglutinin 1(UEA-1) binding of megakaryocytes in bone marrow biopsy specimens: demonstration of heterogeneity in staining pattern reflecting the stages of differentiation. Hematopathol Mol Hematol,1996,10(1-2):99-109.
[305]Barsotti MC, Magera A, Armani C, et al. Fibrin acts as biomimetic niche inducing both differentiation and stem cell marker expression of early human endothelial progenitor cells. Cell Prolif,2011,44(1):33-48.
[306]施森,何延政,宋丽,等.血管内皮生长因子在鼠尾胶原凝胶诱导三维血管新生中的作用研究.2010;14(16)：2879-2882.
[307]AsaharaT, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res,1999,85(3):221-228.
[308]Werner N, Junk S, Laufs U, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res, 2003(1),93:e17-e24.
[309]Morgan R, Kreipke CW, Roberts G, et al. Neovascularization following traumatic brain injury:possible evidence for both angiogenesis and vasculogenesis. Neurol Res,2007,29(4):375-381.
[310]Moubarik C, Guillet B, Youssef B, et al. Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem Cell Rev, 2011,7(1):208-220.
[311]Umemura T, Higashi Y. Endothelial progenitor cells:therapeutic target for cardiovascular diseases. J Pharmacol Sci,2008,108(1):1-6.
[312]Su Y, Zheng L, Wang Q, et al. The PI3K/Akt pathway upregulates Idl and integrin a 4 to enhance recruitment of human ovarian cancer endothelial progenitor cells. BMC Cancer,2010,10:459.
[313]Gao D, Nolan DJ, Mellick AS, et al. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science,2008,319(5860): 195-198.
[314]王秀志,张莉,蔡绍皙,等.电针对脑缺血再灌注大鼠缺血局部脑血管形成的影响.针灸临床杂志,2010,26(08)：61-63.
[315]黄帝内经素问[M].北京：中医古籍出版社,1997：52.
[316]明·杨继洲原著.靳贤补辑重编.黄龙祥整理.针灸大成[M].北京：人民卫生出版社,2007：387.
[317]清·吴亦鼎撰.阎寿峰初校.神灸经纶.北京：人民卫生出版社,1983：81.
[318]Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium. Circulation,1986,74 (5):1124-136.
[319]Szekeres L. Drug-induced delayed cardiac protection against the effects of myocardial ischemia. Pharmacol Ther,2005,108(3):269-280.
[320]钟旭,潘珊珊.运动预适应对大鼠急性心肌缺血损伤早期保护作用的研究.中国运动医学杂志,2009,28(3)：262-266.
[321]Liebelt B, Papapetrou P, Ali A, et al. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience,2010, 166(4):1091-1100.
[322]Gross GJ. Remote preconditioning and delayed cardioprotection in skeletal muscle. Am J Physiol Regul Integr Comp Physiol,2005,289(6):R1562-1563.
[323]Meybohm P, Zacharowski K, Cremer J, et al. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial-the RIPHeart-Study. Eur Heart J,2012, 33(12):1423-1426.
[324]Khaliulin I, Clarke SJ, Lin H, et al. Temperature preconditioning of isolated rat hearts--a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore. J Physiol,2007,581(Pt3):1147-1161.
[325]熊英,顾一煌,吴云川.针灸预处理的心肌保护研究进展及应用前景.中国运动医学杂志,2012,31(10)：926-930.
[326]李晓泓,张露芬,解秸萍.针灸预处理的研究概况与思考.中国临床康复,2005,9(25)：186-187.
[327]崔丽,孙国杰,周华,等.针灸预刺激对阿尔茨海默病模型大鼠学习记忆能力及海马区SOD和NOS的影响.湖北中医学院学报,2009,11(3)：6-8.
[328]柯红,孙国杰,周华.针灸预刺激对AD大鼠脑内自由基影响的实验研究.湖北中医学院学报,2009,11(2)：14-16.
[329]豁银成,孙国杰,杜艳军.针灸预刺激对AD大鼠神经元凋亡相关蛋白Bcl-2、NF-κB的影响.湖北中医学院学报,2010,12(2)：16-18.
[330]Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med,2003, 348(7):593-600.
[331]Galimi F, Summers RG, van Praag H, et al. A role for bone marrow-derived cells in the vasculature of noninjured CNS. Blood,2005,105(6):2400-2402.
[332]Zhang ZG, Zhang L, Jiang Q, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res,2002,90(3):284-288.