抑制基质金属蛋白酶-9可延长大鼠脑栓塞后尿激酶溶栓时间窗

目的研究基质金属蛋白酶抑制剂强力霉素和三七皂甙对大鼠脑栓塞后不同时间尿激酶静脉溶栓效果及并发症的干预作用,评价基质金属蛋白酶抑制剂对尿激酶溶栓治疗时间窗的干预效果。方法采用大鼠自体血栓塞大脑中动脉闭塞(MCAO)模型,分别用免疫组织化学法、TTC染色、伊文氏蓝法和分光光度计法对基质金属蛋白酶-9(MMP-9)、脑梗死体积、血脑屏障通透性和脑出血量进行检测。结果相应时间段尿激酶(UK)溶栓组与缺血对照组比较MMP-9表达显著增高,血脑屏障通透性和脑出血量均有增加趋势,以12h UK组明显;6h UK组较缺血对照组脑梗死体积明显降低。强力霉素和三七皂甙联合尿激酶治疗的各组与相应时间点单用尿激酶组比较MMP-9表达显著降低,脑梗死体积明显下降,血脑屏障通透性和脑出血量均有改善。结论基质金属蛋白酶抑制剂联合溶栓治疗,提高溶栓疗效,减轻溶栓后血脑屏障破坏和出血性转化,可能有延长溶栓治疗时间窗的作用。

Inhibition of matrix metalloproteinase-9 can prolonging urokinase thrombolytic time window after embolic stroke in rats

Objective To evaluated whether the matrix metalloproteinases inhibitor affected the urokinase thrombolytic time window,we study the effect and complication of the matrix metalloproteinase inhibitor doxycycline or panax notoginseng saponins(PNS) on the urokinase thrombolytic therapy at different time after embolic stroke in rats.Methods A cerebral ischemia of rats were established by embolizing left middle cerebral artery with autologous blood clots.The expression of MMP-9 was detected with immunohistochemical staining,TTC staining were applied to detect the infarction volume,the permeability of the observed brain-blood barrier was detected with Evan's blue and the cerebral hemorrhage was quantified with spectropjotometer assay.Results There were increased MMP-9 expression,the permeability of the brain-blood barrier and the cerebral hemorrhage content with urokinase treatment.And there were obviously increased at more than 6 hour after ischemic stroke,and the infarction volume was decreased with urokinase treatment at the 6th hour.After urokinase combined with doxycycline or PNS treatment the expression of MMP-9 was obviousely decreased and the permeability of brain-blood barrier and the infarction volume were decreased.Conclusion The MMPs inhibitor doxycycline or PNS combined with urokinase attenuates thrombolytic-induced the expression of MMP-9,the breakdown of brain-blood barrier and the cerebral infarction volume.The MMPs inhibitor may be enhanced the effect of urokinase thrombolysis and delayed the thrombolytic time window.