Comparative Study Of Rt-PA And Urokinase On The Expression Of MMP-9 And Hemorrhagic Transformation In Stroke

Objective To observe the changes of the expression of matrix metalloproteinase-9 (MMP-9) and the permeability of the brain-blood barrier after ischemia. and to study the influence of rt-PA and urokinase on the expression of MMP-9 and hemorrhagic transformation after thrombolysis therapy in rats,and the relation between MMP-9 and hemorrhagic transformation.Methods A focal cerebral ischemia model of rats were established by embolizing left middle cerebral artery with autologous blood clots. All rats were distributed randomly into four groups: sham-operated group, ischemia group, rt-PA thrombolysis group and urokinase thrombolysis group. rt-PA and urokinase was intravenously given 6 hours after ischemia at a dose of 10mg/kg and 4000u/kg. All rats were killed after 24h ischemia. The expression of MMP-9 was detected with immunohistochemical staining and cerebral hemorrhage was quantified with spectrophotometer assay. And use pathologic methods,TTC staining to detect pathologic changes of the brain and the infarction volume.Results Compared with ischemia group histopathological changes were alleviated in focal ischemia zone in both thrombolysis group with rt-PA and urokinase. The expression of MMP-9, brain water content and the permeability of the brain-blood barrie of the ischemia group were significantly increased after ischemia for 24 hours. The results were 84.24±2.66(P<0.05),0.158±0.010(P<0.01),5774.00±1659.70(P<0.05) respectively , and MMP-9 was significantly further increased to 0.225±0.0341 and 0.227±0.022 after rt-PA and urokinase was intravenously given. Infarction volume significant decreased from 32.43±9.93 to 15.51±8.80,17.06±9.73(P<0.05).Quantified intracerebral hemorrhage and hemorrhagic transformation were significantly higher to compared with the ischemic group after thrombolysis with rt-PA and urokinase. However, there is no difference between rt-PA group and urokinase group.Conclusion The expression of MMP-9, brain water weight and the permeability of BBB increased after ischemia. Infarction volume was significantly decreased after thrombolysis with rt-PA and urokinase. thrombolytic treatment further increased the levels of MMP-9 and hemorrhagic transformation after ischemia. The MMP-9 protein expression strongly correlated with Evan's blue content and hemorrhagic transformation. MMP-9 might involved in the disruption of BBB and hemorrhagic transformation after thrombolytic therapy with rt-PA and urokinase.