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不同时间电针干预对实验性脑出血大鼠炎性免疫反应的研究
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摘要
目的
     观察脑出血后血肿周围脑组织炎症因子的动态变化以及不同时间点电针治疗对其的影响,全面了解多种炎症因子在ICH后的作用机制,探讨电针治疗急性脑出血后炎性免疫反应的可能的干预机制。
     方法
     体重为200±20g的健康成年Wistar雄性大鼠,随机分为4大组:正常组、假手术组、模型对照组、电针治疗组,模型对照组分为5个时间点,即分为造模后6h、24h、48h、72h、8天五个小组;电针治疗组,即将电针治疗组分为6h、24h、48h、72h四个小组。正常组不做任何处理,假手术组造模时用生理盐水代替胶原酶Ⅶ进行造模,模型对照组和电针治疗组采用0.5u胶原酶Ⅶ注射大鼠尾壳核进行造模,确定造模成功后电针治疗组开始做治疗,分别于造模后相应的时间点开始针刺,取“水沟”、“百会”、“足三里”(双侧),接G6805—2型电针仪,疏密波,强度1mA,每次留针30min,每日电针一次,连续电针治疗5次。模型对照组不做治疗,在造模后的6h、24h、48h、72h、8天相应的时间点取材,电针治疗组分别在造模后相应时间开始做治疗,分别连续治疗5天后取材,进行相关指标的检测。应用干湿法检测血肿周围脑组织的含水量,用HE染色观察血肿周围组织形态学的变化,分别用免疫组化和western-blot检测ICAM、MMP-2、MMP-9、TIMP-1的表达。
     结果
     (1)HE染色结果:正常组和假手术组可见丰富的神经细胞,排列整齐,核仁清晰。6h模型对照组大鼠尾状核血肿区可见大片出血灶及点状出血,红细胞浸润,神经细胞坏死,髓质可见部分片状间质轻度水肿;24h可见大量的空泡,中性粒细胞和淋巴细胞浸润现象,炎症反应明显;48h血肿周围脑组织水肿严重,可见大量小胶质细胞浸润和明显的炎性细胞浸润;72h脑组织内脑组织水肿和细胞间隙空化最为明显,周围可见较多和炎性细胞浸润;8天模型对照组血肿周围轻度水肿;6h电针治疗组脑组织内可见点状出血,细胞间质仍有轻度水肿,可见部分中性粒细胞浸润和胶质细胞;与6h模型对照组比较相似。24h电针治疗组脑组织内可见水肿明显减轻,坏死灶明显缩小、极少量出血,有一定的中性粒细胞浸润。48h电针治疗组,水肿明显减轻,可见少量见中性粒细胞浸润,72h电针治疗组可见水肿基本消失,与8天模型对照组比较有明显的好转。电针治疗能明显减轻炎症反应,减少炎症细胞的浸润。
     (2)脑出血大鼠各时间点脑组织含水量的结果:6h模型对照组脑含水量有一定程度的增加,24h组脑含水量明显增高,72h时含水量达到高峰,在8天时逐渐下降,模型对照组与正常组和假手术组比较有显著性差异(P<0.01),而相应时间点的电针治疗组与模型对照组比较:6h电针治疗组与6h模型对照组比较,差异无统计学意义(P>0.05),与8天模型对照组比较,差异无统计学意义(P>0.05);其余相应时间点的电针治疗组与模型对照组比较有显著性的差异(P<0.01),与8天模型对照组比较有显著性的统计学意义(P<0.01)。除了6h电针治疗组,其余时间点进行电针治疗能明显减轻脑出血大鼠脑组织的含水量,减轻脑水肿。
     (3) ICAM-1免疫组化和免疫印迹结果显示:模型对照组的各个时间点血肿周围组织均有不同程度ICAM-1阳性反应的内皮细胞和神经细胞,脑出血后6h周围血管和神经细胞均有ICAM-1的表达,24h、48h ICAM-1表达持续增加,72h达高峰,至8d仍有较高水平的表达。各电针治疗组与对应时间点的模型对照组ICAM-1的表达比较有显著性的差异(P<0.01),6h电针治疗组与6h模型对照组比较差异有统计学意义(P<0.01),但是作用却是增加了ICAM-1的表达,与8天组比较无统计学意义(P>0.05);其余电针治疗组与对应时间点的模型对照组ICAM-1的表达比较有显著性的差异(P<0.01),与8天组比较有显著性的差异(P<0.05)。除了6h电针治疗组,其余时间点进行电针治疗能降低脑出血后大鼠脑组织中ICAM-1的表达。
     (4)脑组织中MMP-9.TIMP-1表达结果显示:正常组未见明显的MMP-9、 TIMP-1的表达,模型对照组6h可见MMP-9明显表达,24h表达逐渐增强,在48h组达到最高峰,在8天时有少量水平的低表达;模型对照组TIMP-1的表达与MMP-9各组的表达相似。经过电针治疗后,除6h电针治疗组外电针治疗组各时间点MMP-9的表达较模型对照组的各时间点比较都有明显的减少,而TIMP-1表达较模型对照组各时间点比较都有明显的增加。统计学的比较:6h电针治疗组分别与6h模型对照组和8天模型对照组比较都无统计学意义(P>0.05),而其余各电针治疗组与对应时间点的模型对照组的MMP-9、TIMP-1的表达比较,存在着显著性的差异(P<0.01),24h、48h、72h组电针治疗组与8天模型对照组比较都有显著性的差异(P<0.05),电针能降低脑出血大鼠血肿周围MMP-9和升高TIMP-1的表达。
     (5)脑组织中MMP-2表达结果显示:正常组与假手术组MMP-2的表达无明显差别(P>0.05),各模型对照组较假手术组和正常组都有显著性的差异(P<0.01);6h模型对照组可见MMP-2的明显表达,24h持续增高至最高峰,48h-72h逐渐减少,但仍明显高于正常组,8天还有高水平的表达;经电针治疗后,除6h电针治疗组外,其余电针治疗组各时间点MMP2的表达明显的减少,6h电针治疗组分别与6h模型对照组和8天模型对照组比较,MMP-2的表达均无统计学意义(P>0.05);其余电针治疗组与对应时间点的模型对照组MMP-2的表达比较有显著性的差异(P<0.01),与8天模型对照组比较有显著性的差异(P<0.01)。电针能够降低脑出血大鼠血肿周围组织MMP-2的表达。
     结论
     本研究表明在脑出血后的急性期选取百会、水沟、足三里进行电针治疗,除6h电针治疗组外,其余各时间点电针治疗均能明显降低脑出血大鼠血肿周围组织ICAM-1、MMP-9、MMP-2的表达,升高TIMP-1的表达,从而发挥抗脑出血后炎症反应的作用,是针灸具有多靶点、多通道作用于炎症细胞和神经元的结果。
Objective
     By invstergation the dynamic changes of inflammatory factors surrounding hematoma after Cerebral hemorrhage and its impact of electro-acupuncture therapy at different time points, comprehend the mechanism of inflammatory factors atfter ICH, study the possible intervention mechanism about inflammatory immune response of the electroacupuncture treatment after acute cerebral hemorrhage.
     Methods
     Choosing120male Wistar rats were randomly divided into normal group, sham-operated group, model group and EA group, normal group, sham-operated group, with18rats each team, the model groups were divided into6h,24h,48h,72h,8days5points, with18rats each team, EA groups were divided into, with18rats each team. the model groups and EA groups Use the0.5u collagenase VII injected rats caudate nucleus to make the modelof experimental, we applied the baihui、shuigou、zusanli (both sides) for the EA group, In the corresponding time points after modeling6h,24h,48h,72h,the EA begined to Scalp-acupuncture therapy (Continuous-wave frequency of120beats/min, intensity of1mA, the treatment time30min, Once a day, five days in a row.) there wasn't any treatment of other groups.In the corresponding time points rats were killed to detect of relevant indicators, Including to measure the brain water content by dry-wet weigh method and observe the morphological changes of perihematomaby He staining, The others were to measure the protein expressions of I CAM、MMP-2、MMP-9、 TIMP-1by Immunohistochemical and Western blot
     Result
     (1)The results of HE staining indicate:There were no significant swelling of normal group and sham operation group of nerve cells, arranging in neat rows, structural integrity and a clear nucleolus. The model group6h rat caudate nucleus hematoma can be seen large areas of hemorrhage and spotting red blood cell infiltration, necrosis of nerve cells, the medulla visible interstitial part of the sheet with mild edema;24h can be seen a large number of vacuoles, neutrophil and lymphocyte infiltration, inflammation obvious; serious48h hematoma surrounding brain edema, seen a large number of microglia infiltration and inflammatory cell infiltration;72h brain tissue within the brain tissueedema and cell gap cavitation is most evident around can be seen more and inflammatory cell infiltration; eight days of the model group with mild edema around the hematoma;6h EA group of brain tissue seen in spotting, stromal cells, any mild edema, visible part of the neutrophil infiltration and glial cells; with the model group6h is quite similar. Visible edema within the brain tissue of24h EA group significantly reduced necrosis significantly reduced, very small amount of bleeding, certain degree of neutrophil infiltration. 48h EA group, the edema was reduced, visible see a small amount of neutrophil infiltration,72h EA group visible edema disappeared, with the model group, a marked improvement in eight days. EA treatment can significantly reduce inflammation, reduce the infiltration of inflammatory cells.
     (2) The water content of brain of Cerebral hemorrhage rats at each time point tissue indicate:6h model group, brain water content increase,24h, the bleeding side of the brain water content was significantly increased, peaked at72h,24-72h to maintain a high level and then decreased, a significant difference (P<0.01) compared with normalthe corresponding point in time the EA group compared with model group, EA group6h6h model group no significant difference between the rest of the EA of the corresponding point in time with the model group and there was significant sex difference (P<0.01), compared with eight days of model group was statistically significant (P<0.05),6h,24h,72h, the EA group after electro-acupuncture treatment can significantly reduce the water content of brain tissue among the groups no significant sexdifferences.
     (3) ICAM-1immunohistochemistry and Western blot results show: Model groups perihematoma have varying degrees of ICAM-1positive endothelial cells and neurons,6hours after intracerebral hemorrhage around blood vessels and nerve cells are the expression of ICAM-1,24h,48h, ICAM-1expression continued to increase,72hreached the peak at a higher level of expression in the8d any. EA group compared with the corresponding time point of the model group, ICAM-1expression, a significant sex difference (P<0.01),6h group of eight days of the EA group was not statistically significant (P>0.05), EA24h group,48h,72h group and8days group significantly with sex differences (P<0.05), while between EA24h group,48h,72h group group comparison no obvious significant difference (P>0.05), electro-acupuncture can reduce ICAM1expression
     (4) MMP-9、TIMP-limmunohistochemistry and Western blot results show:Normal group, no significant MMP-9, TIMP-1expression, the model control group6h visible significant expression of MMP-9,24h expression gradually increased and reached a peak at48h group, a small amount of low level of expression at day8; model controlgroup of TIMP-1expression and MMP-9expression of each group. After electro-acupuncture treatment in addition to the6h group EA, the EA treatment group time points of MMP-9expression compared with the model control group at each time point comparison has significantly reduced; In addition to the6h group of electro-acupuncture, electro-acupuncture treatment group a TIMP-1expression, the point in time relatively significant increase compared with the model control group at each time point. Statistical comparison:6h group of electro-acupuncture treatment control group6h group and8days respectively, and the model comparisons are not statistically significant (P>0.05), while the rest of the EA group and the corresponding time point of the model control group, MMP-9of TIMP-1of expression exist with significant differences (P<0.01), EA24h group,48h,72h group and8days group has significantly with the nature of the differences (<0.05), electro-acupuncture can reduce the cerebral hemorrhage around the hematoma in rats, MMP-9and increased TIMP-1expression.
     (5) MMP2immunohistochemistry and Western blot results show: Normal group and sham operation group, the expression of MMP-2was no significant difference (P>0.05), each model group compared with the sham group and normal group has a significant sex difference (P<0.01); model control group6h visible MMP-2a significant expression to24h continued to increase to the highest peak,48h-72h gradually reduced, but still significantly higher than the normal group, eight days, there is a high level of expression; after electro-acupuncture therapy, except for electro-acupuncture treatment group6h, and the remaining EAsignificantly reduce the treatment group at each time point MMP2in6h group of electro-acupuncture treatment6h group and8days compared with the model control, MMP-2expression were not statistically significant (P>0.05); the rest of the EA treatment groupcompared with the model control group the corresponding time points of MMP-2expression of differences (P<0.01), compared with eight days of model control group, significant sex differences (P<0.01). EA can reduce intracerebral hemorrhage in rats hematoma surrounding tissue expression of MMP-2.
     Conclution:The study shows that after the acute phase of cerebral hemorrhage, electro-acupuncture treatment has significantly reduce ICAM-1, MMP-9, MMP-2expression and increased TIMP-1expression,So that induced anti-inflammatory response after anti-cerebral hemorrhage, which is the result of acupuncture's multi-target, multi-channel role
引文
[1]邓平,吴晓牧.高血压脑出血病理生理机制研究进展.中华脑血管病杂志(电子版),2010,4(4):267-270.
    [2]Tanaka Y, Marumo T, Shibuta H, et al. Serum S100B, brain edema, and hematoma formation in a ratmodel of collagenase induced hemorrhagic stroke. Brain Res Bull,2009,78 (4-5):158-163.
    [3]Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracereb ral hemorrhage. Lancet Neurol,2006,5 (1):53-63.
    [4]潘新发.脑出血后血肿周围组织炎症反应的研究进展.国际神经病学神经外科学杂志[J],2010,37(3):263-266.
    [5]Aronowski T, Hall CE. New horizons for primary intracerebral hemorrhage treatment:experience from preclinical studies. Neurol ogical Research,2005,27 (3):268-297.
    [6]Peel ing J, Yan HJ, Corbett D, et al. Effect of FK-506 oninflamma tion and behavioral outcome following intracerebral hemorrhage in rat. Exp Neurol,2001,167 (2):341-347.
    [7]Wang J, Tsirka SE. Contribution of extracellular proteolysisand microglia to intracerebral hemorrhage. Neurocrit Care,2005,3(1): 77-85.
    [8]Kogure K, Yamasaki Y, Matsuo Y, et al. Inflammation of the brainafter ischemia. Acta Neurochir,1996,66 Suppl:40-43.
    [9]Fassbender K, Rossol S, Kammer T, et al. ProinflamtoryCytokines in serum of patients with acute cerebral ischemic kineticsof cerection and relation to the extent of brain damage and outcomedisease. J Neurol Sci,1994,122.
    [10]Ott L, McClain CJ, Gillespie CJ, Gillespie M, et al. Cytokines andmetabolic dysfunction after severe head injury. J Neurotrauma, 1994 Oct,11 (5):447-452
    [1]YangJ, Gu Y, et al. Lipopolysaccharide-evoked activationof p38 and JNK leads to an increase in ICAM-1 expression inSchwann cells of sciatic nerves [J]. FEBS J,2007,271:4313-4315.
    [2]HsuWY,ChaoYWTsaiYLetal. Resistin induces monocyte-en-dothelial cell adhesion by increasing ICAM-1 and VCAM-1 expres-sion in endothelial cells via p38MAPK-dependent pathway[J]. JCell Physiol, 2011,226:2181-2188.
    [3]Howard EF, Chen Q, Cheng C, et al. NF-kappa B is activated and ICAM-1 gene expression is upregulated during reoxygenation of human brain endothelial cells [J]. Neurosci Lett,1998,248(3):199-203.
    [4]Brett FM,Mizisin AP, Powell HC, etal. Evolution of neuropathology abnormalities assoeiated with blood brain barrier break do intrans geniemiee expressing inter leukin-6inastrocytes[J]. NeuroPathol ExPNeurol,1995:54:766-775.
    [5]ShenA,YangJ, GuY, eta. 1Lipopolysaccharide-evoked activation Of p38 and JNK leads to an increase in ICAM-1 expression in Schwan ncells of sciatic nerves [J]. FEBS J,2008,275(17):4343-4353.
    [6]周官恩,饶明俐,刘宗超.实验性大鼠尾壳核脑出血后p38MAPK. ICAM-1的动态表达[J].中风与神经疾病杂志,2006,23(3):273-276.
    [7]Roebuck KA, Finnegan A. Reguoation of intercellular adhesion molecule (CD54)gene expression[J]. LeukocBiol,1999,66 (6):876-888.
    [8]李晓芳,苏立凯,代瑞廷,等.对脑出血血肿周围组织病理学改变及ICAM-1表达的研究[J].医学研究与教育,2009,26(4):4-7.
    [9]BrettFM, MizisinAP, PowerHC, etal. Evolution of neuropathology abnormalities associated with blood brain barrier break down intrans geniemiee expressing interleukin-6 inastrocytes [J]. JNeuroPatholExPNeurol,1995:54:766-775.
    [10]ZhangRL, Chopp, MZalogaC,etal. The temporal Profiles of ICAM-1 Protein and mRNA expression after transient MCAe on elusion in the rat [J].BrainRes,1995; 682:188.
    [11]Ott L, Mclain CJ, Gil lespie M, et al. Cytokines and metabolic dys-function after severe head injury [J]. J Neurotrauma,1994, 11:447-472.
    [12]KimJSCytokinesandadhesionmoleeulesinstokeandrelateddiseases [J]. JNeurolSei,1996; 137 (2):69-78.
    [13]Mayne M, Ni W, Yan HJ, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor alpha expression is neuro protective after intracerebral hemorrhage [J].Stroke,2001, 32:240-248
    [14]王复新,刘永刚,黄作义.大鼠脑出血周边组织TNF-α、ICAM-1的表达及NAC对其变化的影响.黑龙江医药科学[J],2006,29(6):1-3.
    [15]周婷,马骏,刘又香.电针对脑出血大鼠IL-6及TNF-a表达影响的实验研究[J].湖北中医学院杂志,2008,12(10):23-24.
    [1]Reponen P, Sahlberg C, Munaut C, etal. High expression of 92-kDType collagenase(gelatinase) in the osteoclast lineage during mouse development[J]. ANN N Yacad Sci,1994,732:472-475.
    [2]Abilleira S, Montaner J, Molina CA, etal. Matrixmetalloprotein as e-9 con-centration after spontaneous intracerebral hemorrhage [J]. J Neurosurg,2003,99(1):65.
    [3]Mun-Bryce S,Wilkerson A,Pacheco B,etal. Depressed cortical e xcitability and elevated matrix metallo proteinases in remote brain regions following intracerebral hemorrhage [J]. BrainRes, 2004,1026 (2):227.
    [4]Cunningham LA,WetzelM, RosenbergGA. Multiple roles forMMPs and TIMPs in cerebral ischemia [J]. GLIA,2005,50(4):329-39.
    [5]何琳琳,王复新,王璇.大鼠脑出血周边组织MMP-2、MMP-9的动态表达及其与脑水肿关系的研究[J].黑龙江医药科学,2005,28(4):4-7.
    [6]MontanerJ, Alvarez-SabinJ, MolinaCA, etal. Matrixmetalloproteina seexpression is related to hemorrhagic transformation after cardioembolic. Stroke [J]. Stroke,2001,32(12):2762-7.
    [7]PlanasAM, Sol e S,Justicia C. Expression and activation ofmatrixmetallo-proteinase-2 and-9 in rat brain after transient focal cerebral ischemia[J]. Neurobiol Dis,2001,8 (5):834.
    [8]NordqvistAC, SmurawaH,MathiesenT. Expression of matrixmetallo-proteinases 2 and 9 inmeningiomas associated with different degrees of brain invasiveness and edema [J]. J Neurosurg,2001,95 (5):839-844.
    [9]田力,刘海峰,滕伟禹.大鼠实验性脑出血后基质金属蛋白酶2和9的表达[J].中国动脉硬化杂志,2006,14(3):221-223.
    [10]Bauer AT, Burgers HF, Rabie T, et al. Matrix metallopro-teinase-9 mediates hypoxia-induced vascular leakage in thebrain via tight junction rearrangement [J]. J Cereb Blood FlowMetab,2010, 30 (4):837-848.
    [11]王复新,何琳琳,张淑萍,等.大鼠脑出血周边组织MMP-9.TIMP-1表达对脑水肿的影响[J].中国临床神经科学,2007,15(5):519-522.
    [12]Me Ginn. Poronnik PG, allery ED. etal.The effeets of high glu eose and atorva statillonen do the lialeellnlatrix Production [J]. Diabet Med.2004,21 (10):1102-1107.
    [13]Cllt CS, Lee KT, Lee MY, etal.Effects of rosiglitazonealo, lea:ldilieonbi:lationwithatol. vastatinonnonrraditiollallllarker sofeardiovasculardiseaseinPatientswithtyPe2diabetes. An:JCardiol ,2006,97 (5):646-650.
    [14]刘胜达.大鼠脑出血后脑组织MMP-2、MMP-9表达及其与脑水肿关系的研究[J].实用心脑肺血管病杂志,2007,15(4):249-251.
    [15]江汉秋,刘群,陈志,等.凝血酶致大鼠脑水肿与脑内MMP-9、MMP-2蛋白表达关系的实验研究[J].中国实验诊断学,2010,14(9):1363-1365.
    [16]邢红霞,李建国,杨晋生,等.阿托伐他汀治疗急性脑出血脑水肿作用机制的探讨[J].山东医药,2007,47(1):12-12.
    [17]周德生,陈艳,胡华,等.安脑平冲汤对大鼠脑出血后脑水肿及MMP-2/9蛋白表达的影响[J].疑难病杂志,2011,10(2):129-131.
    [1]王立新.出血性中风急性期病因病机探讨[J].中医研究,2001,14(1):2—3.
    [2]徐以增,毕臻.古代中风病针灸文献探讨[J].上海针灸杂志,1998,17(3):42.
    [3]赵吉平,王燕平.针灸特定穴位的理论与临床[M].北京:科学技术文献出版社,1998:428.
    [4]丁为国,李丽欣,许红,等.针刺百会穴对急性脑血肿大鼠局部脑血流量的影响[J].上海针灸杂志,2003,22(5):7.
    [5]符文彬,樊莉,莫莉莉,等.针灸对家兔急性脑出血的实验研究[J].中医药学刊,2003,21(10):1787.
    [6]裴海涛.针刺“百会透曲鬓”穴对脑缺血再灌注大鼠脑微血管内皮细胞黏附因子表达的影响[J].中国临床康复,2005,9(21):130-131.
    [7]于晓刚,东贵荣,周景华.针刺对急性脑出血大鼠TNF-α的影响[J].中国针灸,2004,24(6):403.
    [8]刘芳,张国威,邹伟,等.针刺对脑出血大鼠IL-β1表达的影响[J].中国伤残医学,2008,16(04):2-5.
    [9]邹伟,匡洪宇,于学平,等.百会透曲鬓头针疗法对急性脑出血大鼠脑水肿及基质金属蛋白酶9表达的影响[J].中医药信息,2010,27(05):81-84.
    [10]张国威,邹伟,刘芳,等.针刺对脑出血急性期大鼠脑损伤及脑水肿拮抗作用的机理研究[J].针灸临床杂志,2010,26(10):5-6.
    [11]张国威,邹伟,刘芳,等.“百会”透“曲鬓”对急性脑出血大鼠脑组织AQP-4表达影响的实验研究[J].中医药信息,2010,27(3):75-79.
    [12]Suzuki N,Hardebo J E,Kahrstr m J,et al. Selective electrical stimulation of postganglionic cerebrovascular parasympathetic nerve fibers originating from thesphe-nopalating ganglion enhances cortical blood flow in the rat[J].J Cereb Blood Flow Metab,1990,50(8):712-715.
    [13]杜艳军,孙国杰,王述菊,等.电针水沟对脑出血大鼠脑血管神经调节物质影响的实验研究[J].针刺研究,2007,32(6):373-376.
    [14]刘波,唐强,李静,针刺治疗脑缺血性损伤的实验研究[J].中国康复理论与实践,2005,11(7):514-515.
    [15]黄晓卿,陈凌.针刺研究中电针应用状况的文献分析和初步研究[J].中国中医基础医学杂志,2001,7(7):73.
    [16]李庆雯,石田寅夫,郭义.不同频率电针对大鼠坐骨神经损伤后神经组织形态学与骨骼肌肌电图的影响[J].中国针灸,2005,25(3):217-220.
    [17]杨静,熊利泽,王强,等.不同刺激参数及其组合对电针诱导大鼠脑缺血耐受效应的影响[J].中国针灸,2004,24(3):208-212.
    [18]邓平,吴晓牧.高血压脑出血病理生理机制研究进展.中华脑血管病杂志(电子版),2010,4(4):267-270.
    [19]Aronowski J, Hall CE. New horizons for primary intracerebral hemorrhage treatment:experience from preclinical studies [J]. Neurological Research,2005,27 (3):268-297.
    [20]Gong C, Hof f JT, Keep RF. Acute inflammatory reaction fol lowing experimental intracerebral hemorrhage in rat[J]. BrainRes,2000, 871 (1):57-65.
    [21]Wang J, Tsirka SE. Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage [J]. Brain,2005,128 (7):1622-1633.
    [22]Wang J, Tsirka SE. Contribution of extracellular proteolysisand microglia to intracerebral hemorrhage [J]. Neurocrit Care,2005,3 (1):77-85.
    [23]Wang J, Tsirka SE. Tuftsin fragment 1-3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke, 2005,36(3):613-618.
    [24]王萍,王伟.星形胶质细胞凋亡和脑缺血[J].中华神经医学杂志,2006,5(2):212-214.
    [25]Wasserman JK, Zhu X, SchlichterL C. Evolution of the inflammatoryresponse in the brain following intracerebral hemorrhage and effects ofdelayedminocycline treatment [J]. Brain Res,2007,1180:140-154.
    [26]Xue M, Del Bigio MR. Acute tissue damage of thrombin and plasmin into rat striatum[J]. Stroke,2001,32:2164-2169.
    [27]张彤,台立稳,赵桂森.脑出血患者血清和颅内血肿液中白细胞介素4、白细胞介素6含量的研究[J].临床荟萃,2009,24(6):478-480.
    [28]王建祯,金晓烨,工绍谦,等.脑出血血肿冲洗液炎性细胞因子动态变化的意义[J].脑与神经疾病杂志,2007,18(4):271-273.
    [29]林杰,张军,张国华.脑出血血肿周围组织损伤的炎症反应机制[J].国外医学脑血管疾病分册,2004,12(7):517-519.
    [30]Kraus J, Oschmann P, Lei S, et al. High concentrations of sVCAM-1 and sICAM-1 in the cerebrospinal fluid of patients with intracerebral heamorrhage are associated with poor outcome [J].Nouril Neurosurg Psychiatry,2002,73:346-348.
    [31]李晓芳,苏立凯,代瑞廷,等.对脑出血血肿周围组织病理学改变及ICAM-1表达的研究[J].医学研究与教育,2009,4(26):4-7.
    [32]HEO J H, LUCERO J, Matrix Metalloproteinase increase very early during experimental cerebral ischemia [J]. J T cerebra Blood Flow Metab,1999,19 (6):624-633.
    [33]ReponenP, SahlbergC,MunautC,etal.High expression of92-kDType collagenase (gelatinase)in the osteoclast lineage during mouse development[J]. ANN N Yacad Sci,1994,732:472-475.
    [34]MandalM, MandalA,DasS, etal. Clinical implications of matrix metal oproteinases[J]. Molecular and Cellular. Biochemistery, 2003,252(12):305-329.
    [35]刘胜达.大鼠脑出血后脑组织MMP-2、MMP-9表达及其与脑水肿关系的研究[J].实用心脑肺血管病杂志,2007,15(4):249-251.
    [36]江汉秋,刘群,陈志,等.凝血酶致大鼠脑水肿与脑内MMP-9、MMP-2蛋白表达关系的实验研究[J].中国实验诊断学,2010,14(9):1363-1365.
    [37]RosenbergGA, NavratilM. Metalloproteinase inhibition blocks edemain intracerebral hemorrhage in the rat [J].Neurology,1997, 48 (4):921-926.
    [38]Wagner KR, Dean C, Beiler S, etal.Rapid activation of pro inflammatory signaling cascades in perihematomal brain regions in a porcine whitematter intracerbral hemorrhage model [J]. Cereb Blood Flow Metab,2003,23:277.
    [39]ZhaoX, ZhangY, StrongR, et al. Distinct patterns of intracerebralhemorrhage-induced alterations in NF-kappaB subunit, iNOS, and COX-2 expression [J]. Neurochem,2007,101:652-663.
    [40]高宏艳,徐宝林,吴江.头部局部亚低温对实验性脑出血大鼠脑组织TNF-α、NF-κB影响的研究[J].中风与神经疾病杂志,2011,28(11):972-975.
    [41]周爽,徐佳,黄建华,等.电针对大鼠高血压性脑出血血肿周围组织NF-κB、TNF-α表达的影响[J].中医药学刊,2005,23(6):985-986.
    [42]周婷,马骏,刘又香.电针对脑出血大鼠IL-6及TNF-a表达影响的实验研究[J].湖北中医学院杂志,2008,12(10):23-24.
    [43]孔莹,邹伟,刘芳,等.“百会透曲鬓”针刺法对脑出血模型大鼠脑组织IL-6影响的实验研究[J].针灸临床杂志,2009,25(12):34-34.
    [44]王颖,硕士论文:电针对脑出血模型大鼠脑内补体C3-C4介导炎症反应的影响机制研究,湖北中医学院.
    [45]邹伟,王珑,李丹,等.针刺“百会”透“曲鬓”对实验性大鼠脑出 血后灶周组织PAR-1和NF-κBp65表达的影响及其相关性分析[J].中医药学报,2011,15(3):58-60.
    [46]张晓忠,博士论文:“百会”透“曲鬓”对脑出血急性期大鼠MMP-2、 CytC、VCAM-1、NGB影响的实验研究,黑龙江中医药大学.
    [47]相悦丽,李振林,张永利.醒脑开窍针刺法治疗急性脑出血120例疗效观察[J].中国中医药科技,2008,15(3):175.
    [1]唐兴江,余秋群,王玉红,等.早期针刺治疗对小量丘脑出血预后的影响[J].四川医学,2005,26(11):1236-1237.
    [2]张树源,鲍春玲,东贵荣,等.头穴透刺治疗急性高血压性脑出血神经功能缺损的临床研究[J].针灸临床杂志,2005,21(3):12-13.
    [3]邹伟,李丹,于学平,等.针刺治疗急性期高血压脑出血的临床研究[J].中医药信息,2009,5(26):104-105.
    [4]朱文增,郭加利,倪金霞,等.头穴透刺结合康复治疗急性脑出血的临床研究[J].针灸临床杂志,2004,20(6):34.
    [5]郑健刚,杜元灏,石学敏.针刺对急性脑出血模型大鼠局部脑血流量的影响[J].中医杂志,2004,45(9):666—667.
    [6]鲍春龄,李璟,东红升.头穴电针对脑出血大鼠脑组织GLUT-1及其基因表达的影响[J].上海中医药大学学报,2008,22(2):50-54.
    [7]丁为国,李丽欣,许红,等.针刺百会穴对急性脑血肿大鼠局部脑血流量的影响[J].上海针灸杂志,2003,25(5):221-223.
    [8]Inoue I, Chen L, Zhou L, et al. Reproduction of scalp acupunc-ture therapy on strokes in the model rats, spontaneous hypertensiverats-stroke prone (SHR-SP) [J]. Neurosci Letters,2002,333(3):191.
    [9]宋春华,朱文增,张凤春.针刺头穴对脑出血大鼠神经元放电影响的实 验研究[J].中国中医药科技,2003,10(4):222.
    [10]东贵荣,东红升,白妍,等.头穴针刺对急性脑出血大鼠痛反应神经元电活动双向调节的实验研究[J].中国临床康复,2006,10(39)48-50.
    [11]赵桂君,李岩.头穴透刺治疗急性脑出血患者的体感诱发电位观察[J].针灸临床杂志,2009,20(8):26-27.
    [12]纪晓军,何宏,温兆霞,等.头穴针刺对大鼠急性期脑出血血脑屏障影响的实验研究[J].中国急救医学,2001,21(11):624.
    [13]于晓刚,东贵荣,周景华.针刺对急性脑出血大鼠TNF-α的影响.中国针灸,2004,24(6):403.
    [14]刘芳,张国威,邹伟,李爽.针刺对脑出血大鼠IL-1β表达的影响[J].中国伤残医学.2008,16(04):2-5.
    [15]邹伟,匡洪宇,于学平,等.“百会”透“曲鬓”头针疗法对急性期脑出血大鼠脑水肿及基质金属蛋白酶9表达的影响[J].中医药信息,2010,27(05):81-84.
    [16]张国威,邹伟,刘芳,等.针刺对脑出血急性期大鼠脑损伤及脑水肿拮抗作用的机理研究[J].针灸临床杂志,2010,26(10):5-6.
    [17]张国威,邹伟,刘芳,等.“百会”透“曲鬓”对急性脑出血大鼠脑组织AQP-4表达影响的实验研究[J].中医药信息,2010,27(3):75-79.
    [18]张国威,邹伟,刘芳,等.针刺对急性脑出血大鼠脑组织GDNF表达影响实验研究[J].内蒙古民族大学学报(自然科学版),2010,25(2):191-193.
    [19]邹伟,刘芳,孙晓伟,等.头针对急性脑出血大鼠BDNF和NGF表达的影响[J].中医药学报,2010,20(12):325-327.
    [20]邹伟,张国威,匡洪宇,等.针刺对急性期脑出血大鼠脑组织VEGF表达调控的动态研究[J].针灸临床杂志,2010,20(9):57-60.
    [21]刘芳,邹伟,张国威,等.针刺对脑出血大鼠神经生长因子基因表达的影响[J].针灸临床杂志,2007,23(5):44—46.
    [1]邓平,吴晓牧.高血压脑出血病理生理机制研究进展.(中华脑血管病杂志(电子版),2010,4(4):267-270.
    [2]Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol,2006,5(1):53-63.
    [3]Joicea SL, Mydeena F, Couraud PO, et al. Modulation of blood-brain barrier permeability by neutrophils:in vitro and in vivo studies[J]. Brain Res,2009,1298:13-23.
    [4]Aronowski J,Hall CE. New horizons for primary intracerebral hemorrhage treatment:experience from preclinical studies [J]. Neurological Research,2005,27 (3):268-297.
    [5]chellinger PD, Fiebach JB, Hoffmann K, et al. Stroke MRIin intracerebral hemorrhage is there peri-hemorhagic penumbra [J] . Stroke,2003,34:1674-1679.
    [6]Tayal AH, Gupta R, Yonas H, et al. Quantitative Perihema—tomal blood flow in spontaneous intracerebral hemorrhage predicts in hospital functional outcome[J]. Stroke,2007,38:319-324.
    [7]朱立新,冯林波,孙增晋.急性脑出血患者局部脑血流量的研究[J].中国医药导报,2007,4(23):110-111.
    [8]张魁灵,袁春兰.脑出血患者血液流变学分析[J].菏泽医学专科学校学报,2005,17(4):55-56.
    [9]高慧娟,黄永勤,王宏伟,等.急性脑出血患者血液流变学改变的临床研究[J].微循环学杂志,2005,15(4):48-51.
    [10]ArdizzoneTD,Lu A, WagnerKR, et al. Glutamate receptor block-ade attenuates glucose hypermetabolism in perihematomalbrain after experimental intracerebral hemorrhage in rat[J]. Stroke, 2004,35(11):2587-2591.
    [11]丰宏林,石冬梅,王德生,等.局部亚低温治疗急性脑出血的临床研究[J].中华医学杂志,2002,82(23):1622-1624.
    [12]Nakamura T, Xi G, Park JW, et al. Holo-transferrin and thrombincan interact to cause brain damage [J]. Stroke,2005,36 (2):348-352.
    [13]Hua Y, Keep RF, Hoff JT, et al. Brain injury after intrace-rebral hemorrhage:the role of thrombin and iron. Stroke,2007,38 (2 Supply):759-762.
    [14]Xi G, ReiserG, Keep RF. The role of thrombin and thrombinreceptors in ischemic, hemorrhagic and traumatic brain injury:deleterious or protective[J]?Neurochem,2003,84 (1):3-9.
    [15]Wu G, Xi G, Huang F. Spontaneous intracerebral hemorrhagein humans:hematoma enlargement, clot lysis, and brain edema [J]. Acta Neurochir (W ien),2006,96 (suppl):78-80.
    [16]Wu J,Hua Y, Keep RF,et al. Iron and iron-handling proteins in the brain after intracerebral hemorrhage [J]. Stroke,2003,34 (12): 2964-2969.
    [17]CHAO G, JU LIAN. T H, RICHARD F K. Acute inflammatory reaction following perimental intracerebral hemorrhage in rat. Brain Res,2000,871(12):57-65.
    [18]MatsushitaK, MengW, WangX, eta.1 Evidence forapoptosis afterintercerebralhemorrhage in ratstriatum[J]. JCereb Blood FlowMetab,2000,20 (12):396-404.
    [19]王景周,周中和,李玮,等.大鼠脑出血血肿周边组织细胞凋亡的动态变化规律研究[J].中国临床神经科学,2003,11:124-127.
    [20]QureshiAI, SuriMF, Ostrow PT, etal. Apoptosis as a form of celldeath in intracerebral hemorrhage [J]. Neurosurgery,2003,52: 1041-1047.
    [21]WangX, AsahiM, Lo EH. Tissue type plasminogen activator am-plifies hemoglobin-induced neurotoxicity in rat neuronal cultures [J]. NeurosciLett,1999,274:79-82.
    [22]Gingrich MB, Junge CE, Lyuboslavsky P, et a.l Potentiation ofNMDA receptor function by the serine protease thrombin [J]. JNeuros-c,2000,20:4582-4595.

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