两种脑出血动物模型的制备和比较研究

Construction and Comparison of Two Animal Models of Cerebral Hemorrhage

目的本研究制备两种脑出血动物模型:脑缺血后使用t PA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(c ICH),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(t PA,10mg/kg)制备脑缺血后出血转化模型;c ICH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;c ICH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t PA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c ICH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。

Objective To construct two animal models of cerebral hemorrhage： tPA - induced cerebral ischemia hemorrhagic trans- formation （MCAO -HT） model and eollagenase- 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 transforma- tion. eICH 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, hem- orrhage inflammation levels had increased significantly in cICH model mice at 24 hours after surgery. Conclusion MCAO - HT model in- duced bleeding functioned by tPA - induced increasing of BBB permeability, which might be better for blood - brain barrier and vascular permeability study. Bleeding of elCH 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.