目的：探讨MMP-9在大鼠脑缺血性损伤中的作用以及替米沙坦对MMP-9表达的调控机制。方法线栓法建立大鼠右侧大脑中动脉闭塞（ MCAO）模型。实验大鼠分为假手术组、溶剂对照组、替米沙坦组、替米沙坦＋GW9662组。采用免疫组化、Western blot和qR-T PCR来观察脑缺血后24 h MMP-9和PPARγ的mRNA和蛋白表达变化，TTC染色评价脑梗死体积，干湿重法评价患侧脑水肿。结果替米沙坦能够明显上调PPARγ，下调 MMP-9表达，改善神经功能缺失，减轻脑水肿，减小梗死体积。 PPARγ特异性阻断剂GW9662能够阻断该作用，保护作用消失。结论 MMP-9在缺血性脑损伤中发挥重要作用，替米沙坦通过激活PPARγ抑制MMP-9表达对脑缺血性脑组织发挥保护作用。%Objective This study is to explore the role of MMP-9 in the focal cerebral ischemia of rats and the mechanisms of telmisartan regulating MMP-9 expression.Methods Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO).SD rats were randomly divided into 4 groups:sham-operated group, vehicle group, telmisartan group, and telmisartan +GW9662 group.At 24h after focal cerebral ischemia,MMP-9 and PPARγexpression were explored by immunohistochemistry, Western blot and qR-T PCR.The brain edema was measured by dry-wet weight method, the infarct volume was detected by TTC stain.Results Telmisartan dramatically increased PPARγand decreased MMP-9 and alleviated the neurological deficits,brain water content and infarct volume after focal cerebral ischemia, which were all reversed by GW9662 administration.Conclusion MMP9-plays an important role in the second brain damage after focal cerebral ischemia.Telmisartan protects brain againsts ischemia by decreasing MMP-9 via activating PPARγ.
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