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 / 国际脑血管病杂志

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 made MCAO,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 tetrazolium 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 zymography and Western blot,respectively.Results Compared to the MCAO group,the neurological function was improved significantly in the rt-PA thrombolysis group,and the infarct volume was also reduced significantly (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.