猴局部脑缺血模型的建立及t-PA溶栓效果的评价

Evaluation of Effect of t-PA in the Model of Monkey Cerebral Ischemia Occlusion

目的探讨猴脑缺血模型的建立及组织型纤溶酶原激活剂(t-PA)在该模型中的溶栓效果。材料与方法对21只成年食蟹猴,术前做CT平扫及介入血管造影排除脑血管及颅内病变,行介入法于大脑中动脉注入自体血栓造成大脑中动脉血栓栓塞(MCAo);再经介入血管造影和CT灌注扫描证明栓塞成功,术后30mic颈内动脉t-PA灌注溶栓,术后2h再次做CT灌注扫描和(或)介入血管造影确认溶栓成功,术后14天连续观察行为学表现。结果21只实验动物中,3只手术前发现病变,未行手术(占14.3%)。18只进行手术的动物中,共有17只DSA及CT灌注扫描证实栓塞成功,成功率94.4%,1只栓塞后介入血管造影及CT灌注扫描均未发现明显缺血,动物麻醉复苏后无脑缺血的行为学表现,占5.6%。17只栓塞成功的动物中13只发现明显血管闭塞、消失(占76.5%),4只表现为部分血管分支显影不良(占23.5%),1只由于栓塞体积过大死亡,1只手术后因穿刺部位出血而死亡,手术死亡率为11.1%。将栓塞术成功并存活的15只动物随机分成两组,8只作为假治疗组;7只为溶栓组,其中1只由于溶栓后颅内出血死亡,溶栓后死亡率为14.3%。MCAo后CT灌注扫描可见缺血区对比剂平均通过时间(MTT)明显增高,和对侧相同区域比较有明显差异。结论(1)血管介入法导入自体血栓制作猴脑缺血模型,手术创伤小,能降低动物的死亡率,增加手术的稳定性;(2)t-PA溶栓治疗脑缺血可以增加脑血流量,改善神经功能。

Objective To discuss the model establishment of monkey cerebral ischemia occlusion （MCAo） and effect of t-PA. Materials and Methods 21 monkeys were performed with CT and DSA to exclude intracranial vascalar disease, 10 - 20cm thrombus were injected into MCA, and tPA were injected after 30min ischemia through Internal Carotid Artery （ICA） by interventional radiological technique, their distribution, effects on cerebral blood flow and neurological deficit were evaluated. Results 3 monkeys had vascular diseases before operation, models were established successfully in 17 of 18 monkeys （94.4%）. vessels were obviously occluded in 13 of 17 monkeys （76.5%） , vessels were not depicted in 4 monkeys, 1 monkey was dead due to seriously embolization, the another was dead due to hemorrhage in puncture site （ 11 . 1% ） . 15 successful models were randomly divided into two groups including 8 monkeys as control and 7 as therapy group. MTT was obviously increased in ischemia area on CT perfusion with significant difference compared to contralateral area. Conclusion Fibrin embolic MCAo model is a noninvasive method, treatment of t-PA can increase cerebral blood flow and relieve neurological deficit.