尿激酶溶栓对大脑中动脉血栓栓塞模型大鼠MMP-9、血脑屏障通透性和脑出血的影响

目的 观察栓塞性脑缺血后及应用尿激酶(urokinase,UK)溶栓后基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达及对脑出血量和血脑屏障通透性的影响,探讨MMP-9与血脑屏障通透性和溶栓后脑出血之间的关系.方法 通过颈动脉内注射自体血制作大鼠血栓栓塞性大脑中动脉闭摩模型,缺血6h后静脉应用UK,24 h后分别采用免疫组化法检测脑组织MMP-9表达、伊文思蓝渗出法检测血脑屏障通透性、TTC染色法检测脑梗死体积、分光光度法检测脑出血量.结果 脑缺血组MMP-9表达显著高于假手术组(P＜0.01),UK溶栓组显著高于脑缺血组(P＜0.01).脑缺血组伊文思蓝含量为(5774.00±1659.70)ng/g,显著高于假手术组的(643.33±151.34)ng/g(P＜0.01),UK溶柃组为(6283.83±1099.28)ng/g,有高于脑缺血组的趋势.UK溶柃组和脑缺血组脑出血量分别为(3.16±8.84)μl(中位数±四分位数)和(0.00±1.48)μl,脑出血发生率分别为25.00%和4.17%.结论 UK溶栓可能上调 MMP-9表达,MMP-9表达与BBB通透性增加与溶栓后脑出血有关.

Effects of urokinase thrombolysis on matrix metalloproteinase-9,blood-brain barrier permeability and intracerebral hemorrhage in a rat model of middle cerebral artery thromboembolism

Objective To observe the effects of the expressions of matrix metalloproteinase-9(MMP-9),intracerebral hemorrhage volumae and blood-brain barrier permeability after embolic cerebral ischemia and thrombolysis with urokinase(UK)and to investigate the relationship between MMP-9 and blood-brain barrier permeability and intracerebral hemorrhage after thrombolysis. Methods A rat model of middle cerebral artery occlusion was established by intracarotid injection of autologous blood clots.UK was given intravenously at 6 hours after ischemia. After 24 hours. the expressions of MMP-9 in brain tissue, blood-brain barrier permeability, cerebral infarct volume, and intracerebral hemorrhage volume were detected by the immunohistochemical method, Evans blue extravasation method, TTC staining method, and spectrophotometric method,respectively. Results The expressions of MMP-9 in a cerebral ischemic group were significantly higher than those in a sham-operation group(P＜0.01),and in the UK group they were significantly higher than those in the cerebral ischemic group (P＜0.01).The Evens blue content in the cerebral ischemic group was 5774.00±1659.70 ng/g, which was significantly higher than 643.33±151.34 ng/g in the sham-operation group (P＜0.01),and in the UK group was 6283.83±1099.28 ng/g, there was a tendency higher than in the cerebral ischemic group. The intracerebral hemorrhage volumes in the UK and cerebral ischemic groups were 3.16±8.84μl(median±quartile)and 0.00±1.48μl, respectively, and the inciderices of intracerebral hemorrhage were 25.00%%and 4.17%.respectively.Conclusions UK thrombolysis may upregulate the expressions of MMP-9.and its expressions are associated with the increased blood-brain barrier permeability and intracerebral hemorrhage after thrombolysis.