Effects of rt-PA intravenous thrombolysis on blood-brain barrier permeability, the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats

Abstract

Objective To investigate the effects of recombinant tissue plasminogen activator （rt-PA） intravenous thrombolysis on blood-brain barrier （BBB） permeability, the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats. Methods A total of 40 adult male Sprague-Dawley rats were allocated into 3 groups： Sham operation group （n = 10）, middle cerebral artery occlusion （MCAO） group （n = 18）, and rt-PA thrombolysis group （n = 18）. A MCAO model was established by using autologous thromboembolism. The sham operation group did not inject any thromboembolus, the MCAO group only madeMCAO, and the rt-PA thrombolysis group received intravenous thrombolysis with rt-PA at 3 hours after MCAO. Brain infarct volume was determined by 2, 3, 5-triphenyl tetrazolimn chloride staining BBB permeability was measured by Evans blue dye leakage. The activities and the expressions of MMP-2 and MMP-9 in brain tissue were detected by Gelatin zymogaphy and Western blot, respectively. Results Compared to the MCAO group, the ne~ological function was improved sigaificantly in the rt-PA thrombolysis group, and the infarct volume was also reduced si~aificantly （t = 7. 365, P = 0. 005）. However, the hemorrhage score （t = - 3. 286, P = 0. 017） and BBB permeability （t = - 3. 947, P = 0. 029） were increased significantly. The activities and the expressions of MMP-2 and MMP-9 in the sham operation group were lower. The activities and the expressions of MMP-2 （t = -45. 121, P = 0. 000; t = -11. 624, P = 0. 000） and MMP-9 （t= -71.849, P= 0.000; t= -8. 992, P= 0. 000） in the MCAO group were increased and upregulated significantly. Compared to the MCAO group, the activities and the expressions of MMP-2 （t = - 28. 792, P = 0. 000; t = -3. 809, P =0. 013） and MMP-9 （t = -53.506, P =0. 000; t = -2. 640, P =0. 046） in the rt-PA thrombolysis group were increased and upregulated significantly. Conclusions After rt-PA intravenous thrombolytic therapy, the BBB permeability was increased. The activities and the expressions of MMP-2 and MMP-9 were increased and upregulated. MMP-2 and MMP-9 might participate in the increased BBB permeability, and thus inducing hemorrhagic transformation after rt-PA intravenous thrombolytic therapy in rats with cerebral ischemia. Key words: Tissue Plasminogen Activator; Brain Ischemia; Matrix Metalloproteinase 9; MatrixMetalloproteinase 2; Blood-Brain Barrier; Thrombolytic Therapy; Cerebral Hemorrhage; Disease Models,Animal; Rats