一氧化氮供体偶联的阿司匹林衍生物抗血栓作用研究

Studies on antithrombotic activities of NO donating-aspirin derivatives

目的观察一氧化氮供体偶联的阿司匹林衍生物对血栓形成的影响。方法利用体外抗血小板聚集实验和大鼠动静脉旁路模型、小鼠肺动脉血栓模型观察一氧化氮供体偶联的阿司匹林衍生物对血栓形成的影响。结果在体外抗血小板聚集实验中目标化合物内的Ⅰ1,Ⅰ2,Ⅰ3,Ⅰ9,Ⅰ14,Ⅱ2,Ⅱ5,Ⅱ6,Ⅱ7和Ⅱ8与阴性对照组相比有显著差异,Ⅱ6与阿司匹林和NCX-4016相比有极显著差异。在大鼠动静脉旁路血栓形成实验和小鼠肺动脉血栓实验中,受试药Ⅱ6组的血栓湿重与CMC-Na组相比有极显著差异,且Ⅱ6对凝血系统也有明显影响。结论一氧化氮供体偶联的阿司匹林衍生物Ⅱ6具有抗血栓形成作用。

OBJECTIVE To study the inhibitory effect of NO donating-aspirin derivatives on platelet aggregation and thrombosis. METHODS The ADP-induced platelet aggregation was measured by a muhifanetional aggregation in vitro. In vivo anfithrombic effects of NO donating-aspirin derivatives were evaluated by A-V by pass thrombosis in rats and pulmonary thrombosis in mice.RESULTS In the experiment of platelet aggregation in vitro, the compound Ⅰ1, Ⅰ2, Ⅰ3, Ⅰ9,Ⅰ 14, Ⅱ 2, Ⅱ 5, Ⅱ 6, Ⅱ 7 and Ⅱ8s were more potent than negative control conapound. Ⅱ6 was much more potent than two positive control compound. Compound Ⅱ 6 was far more potent than CMC-Na in vivo. And it also reduced the death rate in mice treated with collegen-adrenalin. CONCLUSION It is demonstrated that Ⅱ 6 owned a inhibitory effect on thrombosis.