关键词: 重组水蛭素, 角叉菜胶, 血栓, 凝血, 小鼠

Abstract: Objective: To investigate the antithrombotic effects of recombinant hirudin and its mechanism. Methods: Sixty male Kunming mice were randomly divided into 6 group (n=10):control group, model group, aspirin (25 mg/kg) group, recombinant hirudinlow, middle and high dose (0.05, 0.1, 0.2 mg/kg) groups.Except mice in control group, 2.5 mg/kg carrageenan was injected intraperitoneallyto mice in the other groups to produce thrombosis on the mice tail. The mice in aspirin group were administrated intraperitoneally 25 mg/kg aspirin, the mice in recombinant hirudinlow, middle and high dose groups were administrated intraperitoneally 0.05, 0.1, 0.2 mg/kg combinanthirudin, the mice in control group and model group were administrated intraperitoneallynormal saline at the same volume respectively at 24 h, 0.5 h before injecting carrageenan and 24 h after injecting carrageenan. The black tail length of mice and the incidence of black tail were observed at 48h after injection of carrageenan; prothrombin time (PT), activated partial thromboplastin time (APTT), tissue plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1), 6-keto-PGF1α, and thromboxane B2 (TXB2) level in mice plasma were determined. Results: As compared with control group, the mice in model group presented tail thrombosis; PT level in plasma was significantly shortened (P<0.01), PAI-1 and TXB2levels in plasma were significantly increased (P<0.01), while the t-PA and 6-keto-PGF1α levels in plasma in model group were significantly decreased (P<0.01). As compared with model group, the thrombus length in the tail was significantly shortened (P<0.05, P<0.01), PT level was obviously prolonged (P<0.01), and the plasma levels of PAI-1 and TXB2 were significantly decreased (P<0.01), while the plasma levels of t-PA and 6-keto-PGF1α were significantly increased (P<0.01)in the mice of recombinant hirudin low dose, middle dose, high dose groups and aspirin group. As compared with aspirin group, the thrombus length in the tail was significantly increased (P<0.05), PT level was obviously shortened (P<0.01), and the plasma levels of PAI-1 and TXB2 were significantly increased (P<0.01)in the mice of recombinant hirudin low dose group; the plasma level of 6-keto-PGF1α was significantly decreased (P<0.01, P<0.05) in the mice of recombinant hirudin low dose and middle dose groups; the plasma levels of PAI-1 and TXB2 were significantly increased (P<0.01, P<0.05)in the mice of recombinant hirudin middle dose group. Conclusion: The recombinant hirudin can fight against thrombosis, its antithrombotic mechanisms may be related to its influence on the exogenous coagulation system and the promotion of fibrinolysis function.

Key words: recombinant hirudin, carrageenan, thrombosis, coagulation, mice