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目的 观察重组组织型纤溶酶原激活剂(rt-PA)对血管再通后基质金属蛋白酶-2(MMP-2)、MMP-9表达的影响以及神经源性丝氨酸蛋白酶抑制剂(neuroserpin,NSP)的干预作用。方法 应用易卒中型肾血管性高血压大鼠复制大脑中动脉缺血模型,缺血3 h后再灌注并静脉注射rt-PA,于预组在应用rt-PA前脑内注射NSP,1天后处死,常规病理检查,并应用免疫组织化学和原位杂交的方法观察MMP-2、MMP-9在脑组织的表达。结果 缺血再灌注后MMP-2、MMP-9表达均升高;应用rt-PA后可见缺血再灌注区有灶性出血及红细胞漏出,同时使MMP-9进一步升高,但对MMP-2影响不大;应用rt-PA的同时使用NSP可以减轻缺血损伤,减少出血的发生,并使升高的MMP-9减少至接近正常水平,但NSP可以使MMP-2表达略有升高。结论 rt-PA溶栓后出血转化的发生可能与MMP-9表达增加有关,溶栓时联合应用NSP可能通过降低rt-PA所致的MMP-9表达上调而减轻溶栓治疗的出血并发症。
Objective To investigate the effect of recombinant tissue plasminogen activator (rt-PA) on the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 after revascularization and the effect of neuroserpin (NSP) ) Intervention. Methods Middle cerebral artery occlusion (MCAO) was induced in rats with stroke-induced renovascular hypertension. Reperfusion and intravenous injection of rt-PA were performed 3 h after ischemia. Sacrificed, routine pathological examination, and immunohistochemistry and in situ hybridization method to observe the expression of MMP-2, MMP-9 in the brain. Results The expression of MMP-2 and MMP-9 were increased after ischemia / reperfusion. After rt-PA was applied, focal hemorrhage and erythrocyte leakage occurred in ischemia-reperfusion area and MMP- 2 had no effect on the ischemia-reperfusion injury. Rt-PA combined with NSP could reduce ischemic injury, reduce the occurrence of hemorrhage and reduce the elevated MMP-9 to near normal levels, but NSP could slightly increase the expression of MMP-2 . Conclusions The occurrence of hemorrhage and transformation after rt-PA thrombolysis may be related to the increased expression of MMP-9. Thrombolysis combined with NSP may reduce the bleeding complications of thrombolytic therapy by decreasing rt-PA-induced MMP-9 expression.