| Objective: The effect and safety of mini-Plasmin (mini-Plm) on thrombosis in vivo were studied, compared with recombinant tissue plasminogen activator (rt-PA) in present paper. Methods: Using the thrombus model of middle cerebral artery occlusion (MCAO) and abdominal arterial thrombosis in rats, femoral arterial thrombosis in dogs, lung embolism and carotid arterial thrombosis in rabbits, human thrombus in vitro, effect of mini-Plm on clot dissolution, applied as an intra-arterial infusion into the thrombus. The effect of mini-Plm on fibrinolytic system in rabbits was also studied in this paper. Bleeding time (BT), Thrombin time (TT), Prothrombin time (PT), Activated partial thromboplastin time (APTT), Fibrinogen (FIB) concentration in plasma were tested after administration. We also observe whether hemorrhage happened by checking the pathological sections of rat brains. Endothelial barrier antigen (EBA) and matrix metalloproteinases-9 (MMP-9) were measured by immunohistochemistry, by which the damage of blood-brain barrier (BBB) was evaluated. Results: The results showed that intra-arterial mini-Plasmin had thrombolytic effect in all models. Moreover, the thrombolytic effect of mini-Plm in high dose was better than rt-PA, excluding in abdominal arterial thrombosis model. There was no significant influence on fibrinolytic system. FIB concentration reduced markedly. No hemorrhage happened in all animals administered with mini-Plm. The damage of BBB decreased and the expression of MMP-9 reduced significantly after administration of mini-Plm.Conclusion: The results suggest mini-Plasmin have thrombolytic effect in many thrombosis models. There is no significant influence to fibrinolytic system, blood clotting system and BBB. It indicates that mini-Plm may not lead to hemorrhage, distinguished from rt-PA in current usage by its striking safety profile.
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