The Influence Of Urokinase Thrombolysis To The Expression Of Matrix Metalloproteinase-9 In Focal Cerebral Ischemia Of Rats

Objective: To explore the action of matrix metalloproteinase-9 (MMP-9) in urokinase (UK) thrombolysis-associated cerebral ischemia-reperfusion injury and hemorrhagic transformation after focal cerebral ischemia in rats and test methods of reducing thrombolysis-associated hemorrhage and brain injury.Methods:Three groups of rats were studied:(l) rats were subjected to embolic focal ischemia by placing homologous blood clots into the middle cerebral artery and received UK(5000U/0.5k g ) at 2 hours after ischemia; (2) rats were subjected to embolic focal ischemia by placing homologous blood clots into the middle cerebral artery and received NS at 2 hours after ischemia; (3) rats received saline at 2 hours after sham operarion.The expression of matrix metalloproteinase-9 of all the groups was analysed by immunohistochemistry at 6h, 24h, 48h, 72h hours after ischemia.The difference of the matrix metalloproteinase-9 expression was investigated among all the groups.Results: (1) MMP-9 expression apeared 6h after ischemia in untreated controls. MMP-9 activity reached maximum levels by 24 hours, then persisted at this level to 72h.(2)UK-treated rats showed higher upregulation of MMP-9 than untreated controls.(3)There was no MMP-9 expression in rats of sham operation.Conclusions: (1) Focal embolic ischemia induced MMP-9 expression,MMP-9 activity reached maximum levels by 24 hours, then persisted at this level to 72h.(2) UK treatment may upregulate levels of MMP-9 after embolic focal cerebral ischemia.(3)The expression of MMP-9 may lead to thrombolysis-associated hemorrhage.