rt-PA与尿激酶溶栓后对MMP-9及脑出血性转化的对比研究

Comparative study on the effect of rt-PA and urokinase on the expression of MMP-9 and hemorrhagic transformation in a rat embolic stroke model

目的:比较重组组织型纤溶酶原激活剂(Recombinant human tissue-type plasiminogen,rt-PA)与尿激酶溶栓后对基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达和脑出血性转化的影响。方法:采用大鼠自体血栓塞大脑中动脉模型,缺血6h后静脉应用rt-PA及尿激酶,24h后处死,脑组织中MMP-9表达采用免疫组织化学法,脑出血量的测定采用分光光度计法。结果:脑缺血后MMP-9表达增加,rt-PA与尿激酶溶栓后MMP-9表达均进一步增加。脑缺血对照组、rt-PA溶栓组及UK溶栓组平均光密度值分别为0.158±0.010、0.225±0.0341、0.228±0.022,差异有统计学意义(P<0.01)。溶栓后两组脑出血发生率及脑出血量均较缺血对照组增加,但两组之间无明显差别。结论:rt-PA与尿激酶溶栓后均可上调MMP-9表达并与出血性转化密切相关。

Objective：To study the influence of rt-PA and urokinase on the expression of matrix metalloproteinase（MMP-9） and hemorrhagic transformation after thrombolysis therapy in rats.Methods：A focal cerebral ischemia model of rat was established through embolization of left middle cerebral artery with autologous blood clots.rt-PA and urokinase were intravenously administrated 6 hours after ischemia at a dose of 10 mg/kg and 4 000 μ/kg.At the 24th hour after ischemia,all rats were killed.The expression of MMP-9 was detected with immunohistochemical staining and cerebral hemorrhage was quantified by spectrophotometer assay.Results：The expression of MMP-9 was increased after ischemia,and MMP-9 was significantly further upregulated after rt-PA and urokinase had been intravenously administrated.The average optical density（AOD） of MMP-9 in the sham operated group was 0.086±0.008,and increased to 0.158±0.010 after cerebral ischemia for 24 hours and then further increased to 0.225±0.034 and 0.228±0.022 in the rt-PA and urokinase thrombolytic therapy groups.Transformation and quantified intracerebral hemorrhage were significantly higher in the therapy groups as compared with the ischemic group.However,there was no difference between rt-PA group and urokinase group.Conclusion：rt-PA and urokinase treatment both increase the levels of MMP-9 after ischemia.MMP-9 might be involved in the hemorrhagic transformation after thrombolytic therapy with rt-PA and urokinase.