两种脑出血动物模型的制备和比较研究
投稿时间:2016-05-19  修订日期:2016-05-26  点此下载全文
引用本文:魏纯纯,王培,缪朝玉.两种脑出血动物模型的制备和比较研究[J].医学研究杂志,2016,45(11):39-44
DOI: 10.11969/j.issn.1673-548X.2016.11.011
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作者单位E-mail
魏纯纯 200433 上海, 中国人民解放军第二军医大学药理学教研室  
王培 200433 上海, 中国人民解放军第二军医大学药理学教研室  
缪朝玉 200433 上海, 中国人民解放军第二军医大学药理学教研室 cymiao@smmu.edu.cn 
基金项目:国家自然科学基金资助项目(81373414,81130061,81422049,81473208);国家“863”青年科学家项目(2015AA020943)
中文摘要:目的 本研究制备两种脑出血动物模型:脑缺血后使用tPA诱导的出血转化模型(MCAO-HT)及胶原酶注射诱导的脑出血模型(cICH),并比较两种出血模型的异同及可能的优缺点。方法 MCAO-HT模型:栓线经颈内动脉入颅,堵塞大脑中动脉,构建线栓法大脑中动脉堵塞模型,堵塞后5h静脉注射组织型纤溶酶原激活剂(tPA,10mg/kg)制备脑缺血后出血转化模型;cICH模型:利用脑立体定位技术,直接向纹状体注射0.05U胶原酶Ⅳ,诱导脑出血模型。结果 MCAO-HT模型小鼠较MCAO模型小鼠,24h患侧半脑血红蛋白含量显著升高,MCAO-HT模型小鼠血-脑脊液屏障(BBB)通透性显著高于MCAO模型小鼠;cICH模型小鼠,较假手术组小鼠,24h神经功能损伤、脑水肿、出血量和炎性水平都有显著升高。结论 MCAO-HT模型引起的出血为tPA诱导BBB通透性增加,导致的“渗血”,可能更适用于对血-脑脊液屏障及血管通透性的研究。而cICH模型引起的出血为胶原酶直接破坏小血管壁导致的“漏血”,可能更适用于出血诱导的水肿、炎性反应、细胞死亡和氧化应激的研究。
中文关键词:脑缺血  出血转化  脑出血  动物模型
 
Construction and Comparison of Two Animal Models of Cerebral Hemorrhage
Abstract:Objective To construct two animal models of cerebral hemorrhage:tPA-induced cerebral ischemia hemorrhagic transformation (MCAO-HT) model and collagenase-induced ICH (cICH) model, and compare the similarities and differences of these two intracerebral hemorrhage models. Methods MCAO-HT model:We built suture MCAO model by blocking of the middle cerebral artery with suture, after five hours, we injected tissue plasminogen activator (tPA, 10mg/kg) intravenously to induce hemorrhagic transformation. cICH model:intracerebral hemorrhage model was induced by stereotaxicion of 0.05U collagenase Ⅳ into the striatum. Results In comparison with MCAO model mice, ipsilateral hemisphere hemoglobin and blood brain barrier (BBB) permeability in MCAO-HT model mice increased significantly at 24 hours after surgery. Compared with sham-operated mice, neurological damage, cerebral edema, hemorrhage inflammation levels had increased significantly in cICH model mice at 24 hours after surgery. Conclusion MCAO-HT model induced bleeding functioned by tPA-induced increasing of BBB permeability, which might be better for blood-brain barrier and vascular permeability study. Bleeding of cICH model caused by collagenase induced small blood vessels rupture, which suggested to be a better method to do the hemorrhage-induced edema, inflammation, cell death and oxidative stimulated research.
keywords:Cerebral ischemia  Hemorrhagic transformation  Intracerebral hemorrhage  Animal model
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