大鼠急性内囊出血对白细胞流变学行为的影响
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摘要
目的
白细胞在血液中的流变行为是其在体内发挥功能的重要病理生理机制。本研究拟从细胞流变学的角度出发,利用动物在体实验的方法,阐明脑出血急性期白细胞的变形性、趋化性和粘附性的变化规律,对该问题的深入阐明不仅可对脑出血时白细胞的功能有崭新的认识,而且对于采取积极有效的干预措施,改善脑出血患者的预后有十分重要的临床意义。
方法
1大鼠自体血内囊出血动物模型的建立:应用48只健康成年雄性Wistar大鼠(清洁级),用10%水合氯醛腹腔注射麻醉后,俯卧位固定在立体定向仪上。颅顶备皮,医用酒精消毒手术区皮肤,正中矢状切口约1.5cm,剥离皮下组织及骨膜,暴露“十字缝”和“人字缝”。根据包新民等著“大鼠脑立体定位图谱”确定右侧内囊后肢位置:前囟后3.3mm,矢状缝右侧3.2mm,垂直进针7.1mm。确定位置后用牙科钻(钻头直径1mm)钻破颅骨,采取二次注血、二次停针法,缓慢注入在大鼠断尾处采取的自体血液0.1ml,建立内囊出血动物模型,假手术只做刺入动作,不注射血液,作为手术对照组。大鼠清醒后采用Berderson评分法进行行为学评价,评分在手术后3h、6h、12h、24h进行。
2大鼠内囊出血后脑组织形态学的观察:不同实验组的大鼠断头处死,小心剥离颅骨,取出完整脑组织,固定在4%多聚甲醛24h。将固定好的脑组织取出放在冰盘上以针孔为中心连续冠状切片(片厚5um)。切片常规脱蜡,HE染色,在光镜下观察病灶处血肿及组织学改变。
3微循环观察:运用微循环显微镜、计算机图像分析系统对大鼠肠系膜后静脉内白细胞的流变行为(趋边、粘附及变形)进行直观研究。通过图像分析系统上回放录像带,选择无分支、长度100μm、直径10～30μm的微血管进行数据分析。
4统计学方法:应用SPSS 15.0医学统计软件包,各组数据结果用(?)±s表示,组间比较均采取方差分析中的SNK法,P＜0.05为差异有显著性。
结果
1实验组不同时期脑组织病理形态在光镜下均可见脑实质内出血灶,圆形或椭圆形,大小不一,低倍视野内遍布红细胞,出血灶边缘脑组织疏松水肿(见图2-5)。ICH后3h,血肿周围即出现部分神经细胞、胶质细胞肿胀,细胞间隙出现大小不等的空泡,少数神经细胞坏死、消失,白细胞浸润。上述病理变化随着血肿形成的时间延长而逐渐严重。
2从脑出血后3h到12h,白细胞沿壁滚动速度明显减慢。白细胞滚动速度从(14.94±4.23)um/s降低到(3.03±0.47)um/s,各组之间比较均有统计学意义(P＜0.05)。
3从脑出血后3h到12h,白细胞粘附数、滚动数显著增多。白细胞粘附数从(2.96±0.33)个/100um增加到(15.29±1.96)个/100um,滚动数从(8.83±0.96)个/min增加到(36.71±1.33)个/min,各组之间比较均有统计学意义(P＜0.05)。
4从脑出血后3h到12h,总体白细胞-内皮细胞接触时间(TLECT)显著延长。TLECT从(2.89±0.24)s增加到(17.24±2.99)s,各组之间比较均有统计学意义(P＜0.05)。
结论
1通过改良后的脑立体定向术可以准确复制大鼠自体血内囊出血动物模型。
2脑出血急性期血肿压迫产生的占位效应、血肿成分及其降解产物的化学毒性作用、血肿腔内炎症反应和炎症因子等因素都可能造成微循环障碍,引起血肿周围组织的继发性损伤。
3脑出血急性期,机体常处于高度应激状态,由于植物神经中枢受损,神经-体液调节功能紊乱而发生应激性溃疡等其它器官的应激性病变。脑出血的刺激对白细胞的生理功能有显著影响,体现在变形性降低、趋化性增强、膜流动性改变以及白细胞数目的增加。微循环障碍是应激性溃疡等疾病发生的重要病理生理机制之一,白细胞的流变行为可直接影响微循环的灌注,同时,微循环障碍也影响了白细胞的流动状态,这种相互作用,在脑出血急性期,随着血肿时间的延长而逐渐增强。白细胞流变行为的异常不仅是ICH后继发性脑损伤的病理机制之一,还参与了应激性溃疡等其它器官应激的病理生理过程。因此,研究急性脑出血后外周血中白细胞流变行为的改变对早期预防和治疗脑出血并发症有重要的临床指导意义。
Objective
Leukocyte rheology is probably playing an important role in the physiology mechanism of leukocytal function, so my work focused on the effects of rheological properties of leukocytes in rats in terms of cellular Rheology. To interpret the deformability, chemotropism and adhesiveness of Leukocyte, It can help us not only know leukocytal function further, but also can provide a new theory for early diagnosis and clinical treatment of intracerebral hemorrhage.
Methods:
1 To make an intracerebral internal capsular hemorrhage animal model: 54 male Wistar rats were used in this experiment. They were positioned in a stereo tactic frame and a cranial burr hole (1 mm) was drilled on the right AF0.1-0.2 mm. 100μl autologous blood was sampled and then infused stereotacticlly into the right internal capsular. About sham control rats, they had only a needle insertion. After the infusion, the needle was removed, the burr hole was sealed with bone wax, the wound was sutured, and the animal was placed in a warm box with free access to food and water. Berderson test was done by a single observer without knowledge of neurological condition. Motor behavior was evaluated using testing each rat at 3h, 6h, 12h and 24h after operation.
2 Morphological observation of brain : After finishing the Preparation of acute hemorrhage animal model, take the brain tissue and fix it with 10% formaldehyde solution. Through HE strain, observe their dynamic pathological changes under the light microscope.
3 Observation of Microcirculation: By use of Microcirculation microscope and computer-image analyses system , pick out the capillary of no branch ,100μm length and 10～30μm diameter, to observe the leukocyte Rheology.
4 Statistical analyses: All the data were analyzed by SNK test with SPSS 15.0 statistical software.
Results
1 The results showed that, the neurological deficit scores were the highest at 12 h and 24h after operation in the Berderson testing method. At all time points, the scores of the Sham-operated rats were lower than that of the ICH rats and significant differences existed between the two groups.
2 The lesion of experiment group was severe than that of the sham group which is irregular or ellipsoidal blood clot, different size, rarefaction, edema on the tissue of perihematoma, A few of neurocyte and gliocyte are cellular swelling. Inequality size of vacuole in the cell spaces, and many of Leukocytes infiltrate. These pathological changes are more severity along with the longer time of haematoma formative.
3 The Rheological properties of leukocytes in the microcirculation of mesentery in rats were changed obviously in intracerebral hemorrhage group than those of the control group. from 3h to 24h group, the rolling velocity slowed, the number of rolling leucocytes and adherence on endothelium increased, and TLECT obviously extended.
Conclusion
1 We can copy the model of intracerebral internal capsular hemorrhage by use of stereo tactic method successfully.
2 Inflammatory infiltration, neuron necrosis, glial hyperplasia and brain edema in haematoma surrounding of experimental ICH rats may be one of the causes of brain edema and neurobehavioral changes.
3 The rheological properties of leukocytes have been changed by intracerebral hemorrhaged stress respond. Microcirculation disturbance is one important pathomechanism of stress ulcer and other disease. The Rheology properties of Leukocytes can impact on microcirculation directly, and the Microcirculation disturbance can impact on leukocytal circulation. The interaction is more and more obviously along with bleeding time. So, study the changes of rheological properties of leukocytes is useful to prevent and treat the complication of brain hemorrhage beforehand.
白细胞在血液中的流变行为是其在体内发挥功能的重要病理生理机制。本研究拟从细胞流变学的角度出发,利用动物在体实验的方法,阐明脑出血急性期白细胞的变形性、趋化性和粘附性的变化规律,对该问题的深入阐明不仅可对脑出血时白细胞的功能有崭新的认识,而且对于采取积极有效的干预措施,改善脑出血患者的预后有十分重要的临床意义。
方法
1大鼠自体血内囊出血动物模型的建立:应用48只健康成年雄性Wistar大鼠(清洁级),用10%水合氯醛腹腔注射麻醉后,俯卧位固定在立体定向仪上。颅顶备皮,医用酒精消毒手术区皮肤,正中矢状切口约1.5cm,剥离皮下组织及骨膜,暴露“十字缝”和“人字缝”。根据包新民等著“大鼠脑立体定位图谱”确定右侧内囊后肢位置:前囟后3.3mm,矢状缝右侧3.2mm,垂直进针7.1mm。确定位置后用牙科钻(钻头直径1mm)钻破颅骨,采取二次注血、二次停针法,缓慢注入在大鼠断尾处采取的自体血液0.1ml,建立内囊出血动物模型,假手术只做刺入动作,不注射血液,作为手术对照组。大鼠清醒后采用Berderson评分法进行行为学评价,评分在手术后3h、6h、12h、24h进行。
2大鼠内囊出血后脑组织形态学的观察:不同实验组的大鼠断头处死,小心剥离颅骨,取出完整脑组织,固定在4%多聚甲醛24h。将固定好的脑组织取出放在冰盘上以针孔为中心连续冠状切片(片厚5um)。切片常规脱蜡,HE染色,在光镜下观察病灶处血肿及组织学改变。
3微循环观察:运用微循环显微镜、计算机图像分析系统对大鼠肠系膜后静脉内白细胞的流变行为(趋边、粘附及变形)进行直观研究。通过图像分析系统上回放录像带,选择无分支、长度100μm、直径10～30μm的微血管进行数据分析。
4统计学方法:应用SPSS 15.0医学统计软件包,各组数据结果用(?)±s表示,组间比较均采取方差分析中的SNK法,P＜0.05为差异有显著性。
结果
1实验组不同时期脑组织病理形态在光镜下均可见脑实质内出血灶,圆形或椭圆形,大小不一,低倍视野内遍布红细胞,出血灶边缘脑组织疏松水肿(见图2-5)。ICH后3h,血肿周围即出现部分神经细胞、胶质细胞肿胀,细胞间隙出现大小不等的空泡,少数神经细胞坏死、消失,白细胞浸润。上述病理变化随着血肿形成的时间延长而逐渐严重。
2从脑出血后3h到12h,白细胞沿壁滚动速度明显减慢。白细胞滚动速度从(14.94±4.23)um/s降低到(3.03±0.47)um/s,各组之间比较均有统计学意义(P＜0.05)。
3从脑出血后3h到12h,白细胞粘附数、滚动数显著增多。白细胞粘附数从(2.96±0.33)个/100um增加到(15.29±1.96)个/100um,滚动数从(8.83±0.96)个/min增加到(36.71±1.33)个/min,各组之间比较均有统计学意义(P＜0.05)。
4从脑出血后3h到12h,总体白细胞-内皮细胞接触时间(TLECT)显著延长。TLECT从(2.89±0.24)s增加到(17.24±2.99)s,各组之间比较均有统计学意义(P＜0.05)。
结论
1通过改良后的脑立体定向术可以准确复制大鼠自体血内囊出血动物模型。
2脑出血急性期血肿压迫产生的占位效应、血肿成分及其降解产物的化学毒性作用、血肿腔内炎症反应和炎症因子等因素都可能造成微循环障碍,引起血肿周围组织的继发性损伤。
3脑出血急性期,机体常处于高度应激状态,由于植物神经中枢受损,神经-体液调节功能紊乱而发生应激性溃疡等其它器官的应激性病变。脑出血的刺激对白细胞的生理功能有显著影响,体现在变形性降低、趋化性增强、膜流动性改变以及白细胞数目的增加。微循环障碍是应激性溃疡等疾病发生的重要病理生理机制之一,白细胞的流变行为可直接影响微循环的灌注,同时,微循环障碍也影响了白细胞的流动状态,这种相互作用,在脑出血急性期,随着血肿时间的延长而逐渐增强。白细胞流变行为的异常不仅是ICH后继发性脑损伤的病理机制之一,还参与了应激性溃疡等其它器官应激的病理生理过程。因此,研究急性脑出血后外周血中白细胞流变行为的改变对早期预防和治疗脑出血并发症有重要的临床指导意义。
Objective
Leukocyte rheology is probably playing an important role in the physiology mechanism of leukocytal function, so my work focused on the effects of rheological properties of leukocytes in rats in terms of cellular Rheology. To interpret the deformability, chemotropism and adhesiveness of Leukocyte, It can help us not only know leukocytal function further, but also can provide a new theory for early diagnosis and clinical treatment of intracerebral hemorrhage.
Methods:
1 To make an intracerebral internal capsular hemorrhage animal model: 54 male Wistar rats were used in this experiment. They were positioned in a stereo tactic frame and a cranial burr hole (1 mm) was drilled on the right AF0.1-0.2 mm. 100μl autologous blood was sampled and then infused stereotacticlly into the right internal capsular. About sham control rats, they had only a needle insertion. After the infusion, the needle was removed, the burr hole was sealed with bone wax, the wound was sutured, and the animal was placed in a warm box with free access to food and water. Berderson test was done by a single observer without knowledge of neurological condition. Motor behavior was evaluated using testing each rat at 3h, 6h, 12h and 24h after operation.
2 Morphological observation of brain : After finishing the Preparation of acute hemorrhage animal model, take the brain tissue and fix it with 10% formaldehyde solution. Through HE strain, observe their dynamic pathological changes under the light microscope.
3 Observation of Microcirculation: By use of Microcirculation microscope and computer-image analyses system , pick out the capillary of no branch ,100μm length and 10～30μm diameter, to observe the leukocyte Rheology.
4 Statistical analyses: All the data were analyzed by SNK test with SPSS 15.0 statistical software.
Results
1 The results showed that, the neurological deficit scores were the highest at 12 h and 24h after operation in the Berderson testing method. At all time points, the scores of the Sham-operated rats were lower than that of the ICH rats and significant differences existed between the two groups.
2 The lesion of experiment group was severe than that of the sham group which is irregular or ellipsoidal blood clot, different size, rarefaction, edema on the tissue of perihematoma, A few of neurocyte and gliocyte are cellular swelling. Inequality size of vacuole in the cell spaces, and many of Leukocytes infiltrate. These pathological changes are more severity along with the longer time of haematoma formative.
3 The Rheological properties of leukocytes in the microcirculation of mesentery in rats were changed obviously in intracerebral hemorrhage group than those of the control group. from 3h to 24h group, the rolling velocity slowed, the number of rolling leucocytes and adherence on endothelium increased, and TLECT obviously extended.
Conclusion
1 We can copy the model of intracerebral internal capsular hemorrhage by use of stereo tactic method successfully.
2 Inflammatory infiltration, neuron necrosis, glial hyperplasia and brain edema in haematoma surrounding of experimental ICH rats may be one of the causes of brain edema and neurobehavioral changes.
3 The rheological properties of leukocytes have been changed by intracerebral hemorrhaged stress respond. Microcirculation disturbance is one important pathomechanism of stress ulcer and other disease. The Rheology properties of Leukocytes can impact on microcirculation directly, and the Microcirculation disturbance can impact on leukocytal circulation. The interaction is more and more obviously along with bleeding time. So, study the changes of rheological properties of leukocytes is useful to prevent and treat the complication of brain hemorrhage beforehand.
引文
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34 Huang F,Xi G,Keep RF,et al.Brain edema after experimental intracerebral hemorrhage:role of hemoglobin degradation products.[J]Neurosurg,2002,96:287-293
35 Wagner KR,Sharp FR,Ardizzone TD,et al.Heme and iron metabolism:role in cerebral hemorrhage.[J]Cerebral Blood Flow Metab,2003,23:629-652
36 Wu J,Hua Y,Keep RF,et al.Iron and iron-handling proteins in the brain after intracerebral hemorrhage.[J]Stroke,2003,34:2964-2969
37 Sansing LH,Kaznatcheeva EA,Perkins CJ,KomaroffE,Gutman FB,Newman GC.Edema after intracerebral hemorrhage:correlations with coagulation parameters and treatment.[J]Neurosurg.2003 May;98(5):985-992.
38 Hua Y,Xi G,Keep R F,et al.Complement activation in the brain after experimental intracerebral hemorrhage.[J]Neurosurg,2000,92(6):1016-1022
39 Xi G,Hua Y,Keep RF,et al.Brain edema after intracerebral hemorrhage:the effects of systemic complement depletion.[J]Acta Neuro chir,2002,81(Suppl):253-256
40 Czerrnak BJ,Lentsch AB,Bless NM,et al.Synergistic Enhancement of Chemokine Generation and Lung Injury by C5a or the Membrane Attack Complex of Complement.American Journal of Pathology,1999,154:1513-1524
41 Suzuki K,Masawa N,Takatama M.The pathogenesis of cerebmvascu2 lar lesions in hypertensive rats[J].Med Electron Microsc,2001,34(4):230-239.
42 Xue M,Del Bigio MR.Acute tissue damage after injections of throm2 bin and plasmin into rat striatum[J].Stroke,2001,32(9):2164-2169.
43 VilaN,ReverterJC,YagueJ,eta interaction between interleukin-6 and then aturalantieoauglantinaeute stroke.[J]InterferoneytokineRes,2000,20:325-329.
44 Lema PP,Girard C,Vachon P.Evaluation of dexamethasone for the treatment of intracerebral hemorrhage using a collagenase - induced intracerebral hematoma model in rats[J].Vet Pharmacol Ther,2004,27(5):321-328.
45 Qureshi A I,SuriMF,Ling GS,et al.Absence of early p roinflammatory cytokine expression in experimental intracerebral hemorrhage[J].Neurosurgery,2001,49(2):416-420.
46 Godoy D,Boccio A,Hugo N.Systemic inflammatory response syn2 drome and primary of spontaneous intracerebral hemorrhage[J].Rev Neurol,2002,35(12):1101-1105.
47 傅琦,刘春风,包仕尧.活化白细胞在脑血管疾病发病中的作用机理[J].国外医学·脑血管疾病分册,1994,2(4):201-203.
48 Power C,Henry S,Marc R,et al.Intracerebral Hemorrhage Induces Macrophage Activation and Matrix Metallo-proteinages.Ann Neurol,2003,53:731-742
49 郑健刚,杜元灏,石学敏.针刺对急性脑出血模型鼠微血管形态学的影响[J].天津中医药,2004,21:368-370.
50 HAN Hong,YU Xue zhong,GUO Shu bin Correlation analysis of cerebral hemorrhage and upper gastrointestinal bleeding Chin J Crit Care Med[J]2007,27(8):920-921
51 张希栓,浅谈白细胞在血液流变性障碍中的作用[J]中外健康文摘2008,5(1):45
52 Brosnan CF,Cannella B,Battbtini L,et al.Cytokine localization in multiple sclerosis lesions:correlation with adhesion molecule expression and reactive nitrogen species[J].Neurology,2005,45(suppl 6):1-21.
53 Cannella B,Raine CS.The adhesion molecule and cytokine profile of multipele sclerosis lesions[J].Ann Neurol,2005,37:424-435.
54 Dore- Duffy P,Newman W,Balabanor R,et al.Circulating,soluble adhesin proteins in cerebrospin al fluid and serum of pationts with multiple sclerosis:correlation with clinical ctivity[J].Ann Neurol,2004,37:55-62.
55 乔正荣.白细胞和血管内皮细胞的粘附作用.重庆医科大学学报,2003,28(1):122-124
56 邢海燕.流动力学作用与血管内皮.[J]微循环学杂志,2002,12(3):42-45
57 Xia L,Sperandio M,Yago T,et al.P-selectin glycoprotein ligand deficient mice have impaired leukocyte tethering to E2selectin under flow.[J]Clin Invest,2002;109:939-950.
58 Barone FL,Hillegass LM,Price WJ,et al Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue:myeloperoxidase activity assay and histologic verification,[J]Neurosci Res,1991,29:336.
59 Mitchell S.V.Elkind,MD,MS;Robert Sciacca,EngScD,et al.Leukocyte count is associated with aortic arch plaque thickness.Stroke,2002,33:2587-2592.
60 Armin J,Grau,MD,et al.Leukocytes count as an independent predictor of recurrent ischemic events.stroke,2004,35:1147-1152.
61 M.S.V.Elkind,MD,MS,et al.Relative elevation in baseline leukocyte count predicts first cerebral infarction.neurology,2005,64:2121-2125
62 Rovlias A,Kotsou S The blood leukocyte count and its prognostic significance in severe head injury.Surg Neurol,2001,55:190-196
63 Xue M,Del Bigio MR.Intracortical hemorrhage injury in rats relationship between blood fractions and brain cell death.Stroke,2000,31:1721-1727
64 Xi G,Keep RF,et al.Complement activation in the brain after experimental intracerebral hemorrhage.[J]Neuro surg,2000,92:1016-1022.
65 Knoblach SM,Faden AI.Administration of either anti- intercellular adhesion molecule - 1 or a nonspecific control antibody improves recovery after traumatic brain injury in the rat[J]Neurotrauma,2002,19(9):1039-1050.
66 Seiffge-D Bissinger-T,Kremer-E et.al Inhibitory effects of Pentoxifyl line on LPS induced leukocyte adhesion and macromolecular extravagation in the microcirculation.[J]Inflame Res.1995;44(7):281-286.
1 程庆儒.白细胞流变学的研究[J].中国微循环,1996,1(1):56-59.
2 骆秉铨,黄荣国,冯小平,等.白细胞呼吸暴发过程细胞流变行为的临床研究[J]中国血液流变学杂志,2001,11(2):891-893.
3 刘宗印,鞠全荣,潘齐川,等.恶性肿瘤病人粒细胞流变性的变化[J].中国现代实用医学杂志,2004,3(2):13-14.
4 Mayrovitz HN,Kang SJ,Herscovici B,et al.Leuko2 eyte adherence inifiaton in skeletal muscle capillaries and venules.Microvasc Res,1987,33:221.
5 姜勇,刘爱华,赵克森。大鼠肠系膜微循环白细胞流动分布的研究.中国病理生理杂志 1998;14(4):347-350
6 病理生理学.主编:石增立.人民军医出版社.
7 严宗毅,魏茂元,于天文.血液流变学.基础应用.哈尔滨:黑龙江科学技术出版社.
8 王维治.神经病学.第四版.北京人民卫生出版社,2002,142-145.
9 Sansing LH,Kaznatcheeva EA,Perkins CJ,Komaroff E,Gutman FB,Newman GC.Edema after intracerebral hemorrhage:correlations with coagulation parameters and treatment.J Neurosurg.2003 May;98(5):985-992.
10 Xi G,Hua Y,Keep RF,et al.Brain edema after intracerebral hemorrhage:the effects of systemic complement depletion.Acta Neuro chir,2002,81(Supply):253-256.
11 张希栓,浅谈白细胞在血液流变性障碍中的作用[J]中外健康文摘2008,5(1):45.
12 乔正荣.白细胞和血管内皮细胞的粘附作用.重庆医科大学学报,2003,28(1):122-124.
13 Xia L,Sperandio M,Yago T,et al.P2selectin glycoprotein ligand212 deficient mice have impaired leukocyte tethering to E2selectin under flow.[J]Clin Invest,2002;109:939-950.
14 Li Z,Xi X,Gu M,et al.A stimulatory role for cGMP-dependent protein kinas in platelet activation.[J]Cell 2003;112:77-86.
15 Xue M,Del Bigio MR.Acute tissue damage after injections ofthrom2 bin and plasmin into rat striatum[J].Stroke,2001,32(9):2164-2169.
16 VilaN,ReverterJC,YagueJ,etal Interaction between interleukin-6 and then aturalantieoauglantinaeute stroke.J Interferoneytokine Res,2000,20:325-329.
17 Lema PP,Girard C,Vachon P.Evaluation of dexamethasone for the treatment of intracerebral hemorrhage using a collagens - induced intracerebral haematoma model in rats[J].Vet Pharmacol Ther,2004,27(5):321-328.
18 钱自奋.红细胞的变形意义及美国测定红细胞变性能力的几种方法细胞流变学 1994.11-121.
19 邢海燕.流动力学作用与血管内皮.[J]微循环学杂志,2002,12(3):42-45.
20 严宗毅.测量红细胞变形性的新方法[J]国外医学·生物医学工程分册,1997,20(5):257-261.
21 谭润鸾,刘成玉,万秀霞,等.缺血性脑血管病白细胞粘附功能和变形能力的变化.青岛医学院学报 1995;3(1):20-22.
22 刘明远,王月燕,刘玫香.急性心肌缺血再灌注对兔白细胞流变学影响及硝苯啶对其保护作用实验研究.中国血液流变学杂志 1997;7(3):8-11.
23 林琳,朱凡河,赵建康.高血压患者白细胞变形性的初步观察.微循环学杂志1997;7(3):32-33.
24 何作云,叶自林,文芳.兔动脉粥样硬化中性白细胞变形性改变的机制.中国微循学.1998;2(3):137-139.
25 林荣军,刘成玉,潘玉娟,等.肺炎患儿白细胞变形能力和粘附功能的变化及临床意义.微循环学杂志 1997;7(1):38-39.
26 刘成玉,李云芳,万秀霞,等.糖尿病性血管病变与白细胞粘附功能和变形能力关系的研究.中国糖尿病杂志 1995;3(2):102-104.
27 赵克森.重症休克时白细胞流变行为的研究进展.微循环学杂志 1997;7(1):12-15.
5 LainezJM,ParejaA.The medical treatment of intracerebral hemorrhage [J].RevNeurol,2000;31(2):174-179.
6 Spirt M J.Acid suppression in critically ill patients:What does the evidence support[J]Pharmacotherapy,2003,23(2):87-93.
7 王金娥.急性脑出血患者白细胞增高的临床意义[J].卒中与神经疾病,1999,6(1):54-55.
8 孔竹青 急性脑出血患者外周血白细胞及中性粒细胞计数变化的临床意义.[J]徐州医学院学报,2007,27(7):459-461
9 Qureshi AI,SuriMF,Ling GS,et al.Absence of early proinflammatory cytokine expression in experimental intracerebral hemorrhage[J].Neurosurgery,2001,49(2):416-420.
10 Godoy D,Boccio A,Hugo N.Systemic inflammatory response syndrome and primary of spontaneous intracerebral hemorrhage[J].Rev Neurol,2002,35(12):1101-1105.
11 陈东亮,谢庆海,彭涛,等.颅脑损伤并发上消化道出血的预防和治疗[J].中国临床神经外科杂志,2006,11(10):607-609.
12 傅琦,刘春风,包仕尧.活化白细胞在脑血管疾病发病中的作用机理[J].国外医学·脑血管疾病分册,1994,2(4):201-203.
13 程庆儒.白细胞流变学的研究[J].中国微循环,1996,1(1):55-59.
14 骆秉铨,黄荣国,冯小平等,白细胞呼吸暴发过程细胞流变行为的临床研究[J]中国血液流变学杂志,2001,11(2):891-893.
15 刘宗印,鞠全荣,潘齐川等,恶性肿瘤病人粒细胞流变性的变化[J].中国现代实用医学杂志,2004,3(2):13-14.
16 Berderson JB,Pitts LH,Tsuji M,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of neurologic examination.[J]Stroke,1986;17:472-476.
17 姜勇,刘爱华,赵克森。大鼠肠系膜微循环白细胞流动分布的研究.[J]中国病理生理杂志1998;14(4):347-350.
18 Gerhard M,Robert W,Rudolf WC,et al.Basal ganglia haematomas in noncomatose patients:sub acute stereo tactic aspiration improves long-term outcome in comparison to purely medical treatment.[J]Neuro surg Rev,2005,28(1):64-66
19 王维治.神经病学.第四版.北京人民卫生出版社,2002,142-145
20 何刚,刘茂才.实验性脑出血动物模型的研究进展.[J]国外医学·神经病学神经外科分册,2001,28(2):80-83
21 Lopez VE,Hamandez LA,Calandre L,et al.Time window for clinical effectiveness of mass evacuation in a rat balloon model mimicking an intraparenchymat0us hematoma[J].Neurol Sci,2000。 174(1):40-46.
22 Deinsberger W,Vogel J,Kuschinsky W,et al.Experimental intracerebral hemorrhage:description of a double injection model in rats.[J]Neurol Res,1996,18:475-477.
23 周中和,曲方,何祥,等。一种改良大鼠自体血脑出血模型:二次注血、退针法。[J]中国临床神经科学。2004,12(4):406-409
24 Misra UK,Kalita J,Pandey S,et al.Predictors of gastrointestinal bleeding in acute intracerebral hemorrhage[J]Neurol Sci,2003,208(1-2):25-29
25 Nath FP,Jenkins A,Mendelow AD,et al.Early homodynamic changes in experimental intracerebral hemorrhage.[J]Neurosurg,1986,65:697-703
26 Li Y,Powers C,Jiang N,et al:Intact,injured,necrotic,and apoptotic cells after focal cerebral ischemia in the rat.[J]Neurol Sci 1998;15(6):119-132
27 Gebel JM,Brott TG,Sila CA,et al.Decreased perihematomal edema in thrombolysis-related intracerebral hemorrhage compared with spontaneous intracerebral hemorrhage.[J]Stroke,2000,31:596-600
28 Wagner KR,Xi G,Hua Y,et al.Lobar intracerebral hemorrhage model in pigs:rapid edema development in perihematomal white matter.[J]Stroke,1996,27(3):490-497
29 Yang GY,Betz AL,Chenevert TL,etal.Experimental intracerebral hemorrhage:relationship between brain edema,blood brain barrier permeability in rats.[J] Neurosurg,1994,81:93-102.
30 Carhuapoma JR,Wang PY,Beauchamp NJ,Keyl PM,Hanley DF,Barker PB.Diffusion-weighted MRI,and proton MR spectroscopic imaging in the study of secondary neuronal injury after intracerebral hemorrhage.[J]Stroke.2000;31:726-732.
31 Stephan A,Mayer MD,Angela Lignelli,MD,et al.Perilesional blood flow and edema formation in acute intmcerebral hemorrhage:A SPECT Study.[J]Stroke,1998;29:1791-1798
32 Kidwell CS,Saver JL,Mattiello J,et al.Diffusion-perfusion MR evaluation of perihematomal injury in hyper acute intracerebral hemorrhage.[J]Neurology,2001,57:1611-1617.
33 Donovan FM,Pike CJ,Cotman CW,et al.Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and Rho A activities[J]Neurosci,1997,17:5316-5326
34 Huang F,Xi G,Keep RF,et al.Brain edema after experimental intracerebral hemorrhage:role of hemoglobin degradation products.[J]Neurosurg,2002,96:287-293
35 Wagner KR,Sharp FR,Ardizzone TD,et al.Heme and iron metabolism:role in cerebral hemorrhage.[J]Cerebral Blood Flow Metab,2003,23:629-652
36 Wu J,Hua Y,Keep RF,et al.Iron and iron-handling proteins in the brain after intracerebral hemorrhage.[J]Stroke,2003,34:2964-2969
37 Sansing LH,Kaznatcheeva EA,Perkins CJ,KomaroffE,Gutman FB,Newman GC.Edema after intracerebral hemorrhage:correlations with coagulation parameters and treatment.[J]Neurosurg.2003 May;98(5):985-992.
38 Hua Y,Xi G,Keep R F,et al.Complement activation in the brain after experimental intracerebral hemorrhage.[J]Neurosurg,2000,92(6):1016-1022
39 Xi G,Hua Y,Keep RF,et al.Brain edema after intracerebral hemorrhage:the effects of systemic complement depletion.[J]Acta Neuro chir,2002,81(Suppl):253-256
40 Czerrnak BJ,Lentsch AB,Bless NM,et al.Synergistic Enhancement of Chemokine Generation and Lung Injury by C5a or the Membrane Attack Complex of Complement.American Journal of Pathology,1999,154:1513-1524
41 Suzuki K,Masawa N,Takatama M.The pathogenesis of cerebmvascu2 lar lesions in hypertensive rats[J].Med Electron Microsc,2001,34(4):230-239.
42 Xue M,Del Bigio MR.Acute tissue damage after injections of throm2 bin and plasmin into rat striatum[J].Stroke,2001,32(9):2164-2169.
43 VilaN,ReverterJC,YagueJ,eta interaction between interleukin-6 and then aturalantieoauglantinaeute stroke.[J]InterferoneytokineRes,2000,20:325-329.
44 Lema PP,Girard C,Vachon P.Evaluation of dexamethasone for the treatment of intracerebral hemorrhage using a collagenase - induced intracerebral hematoma model in rats[J].Vet Pharmacol Ther,2004,27(5):321-328.
45 Qureshi A I,SuriMF,Ling GS,et al.Absence of early p roinflammatory cytokine expression in experimental intracerebral hemorrhage[J].Neurosurgery,2001,49(2):416-420.
46 Godoy D,Boccio A,Hugo N.Systemic inflammatory response syn2 drome and primary of spontaneous intracerebral hemorrhage[J].Rev Neurol,2002,35(12):1101-1105.
47 傅琦,刘春风,包仕尧.活化白细胞在脑血管疾病发病中的作用机理[J].国外医学·脑血管疾病分册,1994,2(4):201-203.
48 Power C,Henry S,Marc R,et al.Intracerebral Hemorrhage Induces Macrophage Activation and Matrix Metallo-proteinages.Ann Neurol,2003,53:731-742
49 郑健刚,杜元灏,石学敏.针刺对急性脑出血模型鼠微血管形态学的影响[J].天津中医药,2004,21:368-370.
50 HAN Hong,YU Xue zhong,GUO Shu bin Correlation analysis of cerebral hemorrhage and upper gastrointestinal bleeding Chin J Crit Care Med[J]2007,27(8):920-921
51 张希栓,浅谈白细胞在血液流变性障碍中的作用[J]中外健康文摘2008,5(1):45
52 Brosnan CF,Cannella B,Battbtini L,et al.Cytokine localization in multiple sclerosis lesions:correlation with adhesion molecule expression and reactive nitrogen species[J].Neurology,2005,45(suppl 6):1-21.
53 Cannella B,Raine CS.The adhesion molecule and cytokine profile of multipele sclerosis lesions[J].Ann Neurol,2005,37:424-435.
54 Dore- Duffy P,Newman W,Balabanor R,et al.Circulating,soluble adhesin proteins in cerebrospin al fluid and serum of pationts with multiple sclerosis:correlation with clinical ctivity[J].Ann Neurol,2004,37:55-62.
55 乔正荣.白细胞和血管内皮细胞的粘附作用.重庆医科大学学报,2003,28(1):122-124
56 邢海燕.流动力学作用与血管内皮.[J]微循环学杂志,2002,12(3):42-45
57 Xia L,Sperandio M,Yago T,et al.P-selectin glycoprotein ligand deficient mice have impaired leukocyte tethering to E2selectin under flow.[J]Clin Invest,2002;109:939-950.
58 Barone FL,Hillegass LM,Price WJ,et al Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue:myeloperoxidase activity assay and histologic verification,[J]Neurosci Res,1991,29:336.
59 Mitchell S.V.Elkind,MD,MS;Robert Sciacca,EngScD,et al.Leukocyte count is associated with aortic arch plaque thickness.Stroke,2002,33:2587-2592.
60 Armin J,Grau,MD,et al.Leukocytes count as an independent predictor of recurrent ischemic events.stroke,2004,35:1147-1152.
61 M.S.V.Elkind,MD,MS,et al.Relative elevation in baseline leukocyte count predicts first cerebral infarction.neurology,2005,64:2121-2125
62 Rovlias A,Kotsou S The blood leukocyte count and its prognostic significance in severe head injury.Surg Neurol,2001,55:190-196
63 Xue M,Del Bigio MR.Intracortical hemorrhage injury in rats relationship between blood fractions and brain cell death.Stroke,2000,31:1721-1727
64 Xi G,Keep RF,et al.Complement activation in the brain after experimental intracerebral hemorrhage.[J]Neuro surg,2000,92:1016-1022.
65 Knoblach SM,Faden AI.Administration of either anti- intercellular adhesion molecule - 1 or a nonspecific control antibody improves recovery after traumatic brain injury in the rat[J]Neurotrauma,2002,19(9):1039-1050.
66 Seiffge-D Bissinger-T,Kremer-E et.al Inhibitory effects of Pentoxifyl line on LPS induced leukocyte adhesion and macromolecular extravagation in the microcirculation.[J]Inflame Res.1995;44(7):281-286.
1 程庆儒.白细胞流变学的研究[J].中国微循环,1996,1(1):56-59.
2 骆秉铨,黄荣国,冯小平,等.白细胞呼吸暴发过程细胞流变行为的临床研究[J]中国血液流变学杂志,2001,11(2):891-893.
3 刘宗印,鞠全荣,潘齐川,等.恶性肿瘤病人粒细胞流变性的变化[J].中国现代实用医学杂志,2004,3(2):13-14.
4 Mayrovitz HN,Kang SJ,Herscovici B,et al.Leuko2 eyte adherence inifiaton in skeletal muscle capillaries and venules.Microvasc Res,1987,33:221.
5 姜勇,刘爱华,赵克森。大鼠肠系膜微循环白细胞流动分布的研究.中国病理生理杂志 1998;14(4):347-350
6 病理生理学.主编:石增立.人民军医出版社.
7 严宗毅,魏茂元,于天文.血液流变学.基础应用.哈尔滨:黑龙江科学技术出版社.
8 王维治.神经病学.第四版.北京人民卫生出版社,2002,142-145.
9 Sansing LH,Kaznatcheeva EA,Perkins CJ,Komaroff E,Gutman FB,Newman GC.Edema after intracerebral hemorrhage:correlations with coagulation parameters and treatment.J Neurosurg.2003 May;98(5):985-992.
10 Xi G,Hua Y,Keep RF,et al.Brain edema after intracerebral hemorrhage:the effects of systemic complement depletion.Acta Neuro chir,2002,81(Supply):253-256.
11 张希栓,浅谈白细胞在血液流变性障碍中的作用[J]中外健康文摘2008,5(1):45.
12 乔正荣.白细胞和血管内皮细胞的粘附作用.重庆医科大学学报,2003,28(1):122-124.
13 Xia L,Sperandio M,Yago T,et al.P2selectin glycoprotein ligand212 deficient mice have impaired leukocyte tethering to E2selectin under flow.[J]Clin Invest,2002;109:939-950.
14 Li Z,Xi X,Gu M,et al.A stimulatory role for cGMP-dependent protein kinas in platelet activation.[J]Cell 2003;112:77-86.
15 Xue M,Del Bigio MR.Acute tissue damage after injections ofthrom2 bin and plasmin into rat striatum[J].Stroke,2001,32(9):2164-2169.
16 VilaN,ReverterJC,YagueJ,etal Interaction between interleukin-6 and then aturalantieoauglantinaeute stroke.J Interferoneytokine Res,2000,20:325-329.
17 Lema PP,Girard C,Vachon P.Evaluation of dexamethasone for the treatment of intracerebral hemorrhage using a collagens - induced intracerebral haematoma model in rats[J].Vet Pharmacol Ther,2004,27(5):321-328.
18 钱自奋.红细胞的变形意义及美国测定红细胞变性能力的几种方法细胞流变学 1994.11-121.
19 邢海燕.流动力学作用与血管内皮.[J]微循环学杂志,2002,12(3):42-45.
20 严宗毅.测量红细胞变形性的新方法[J]国外医学·生物医学工程分册,1997,20(5):257-261.
21 谭润鸾,刘成玉,万秀霞,等.缺血性脑血管病白细胞粘附功能和变形能力的变化.青岛医学院学报 1995;3(1):20-22.
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