一氧化氮供体偶联的阿司匹林衍生物ZA-6的抗血栓作用

目的:研究新型NO-阿司匹林衍生物ZA-6抗血栓作用。方法:采用血小板聚集试验和实验性血栓动物模型,测定ZA-6的抗血栓活性;给予ZA-6后,采用金属镉还原法测定大鼠血浆中NO浓度的变化;采用放免法测定大鼠血浆中环磷腺苷酸(cAMP)和环磷鸟苷酸(cGMP)的含量变化。结果:在不同诱导剂(ADP、花生四烯酸和胶原蛋白)诱导的血小板聚集试验中,ZA-6均能显著抑制血小板的聚集,IC50均低于阿司匹林的IC50(P<0.05)。在大鼠动-静脉旁路模型中,ZA-6高、低剂量组均能明显抑制血栓的形成(P<0.05);在小鼠肺血栓栓塞模型中,ZA-6可以提高小鼠的生存率(P<0.05);在给予ZA-6后,大鼠血浆中NO的浓度明显升高(P<0.05),血浆中cAMP浓度明显升高(P<0.05),但cGMP浓度却没有增加。结论:ZA-6具有较强的抗血栓活性,可能是由于经过体内代谢为阿司匹林和NO发挥协同作用。

Anti-thrombotic effect of compound ZA-6,a novel NO-donating-aspirin derivative

Aim:To study the anti-platelet aggregation and anti-thrombosis as well as the mechanisms of NO-releasing aspirin derivative,compound ZA-6.Methods:The activities of compound ZA-6 were detected using platelet aggregation assay and experimental thrombus animal models.After administration of compound ZA-6,changes to the concentrations of plasma NO (using cadmium reduction method),cAMP and cGMP (using RIA method) were determined.Results: In vitro and ex vivo platelet aggregation assays,compound ZA-6 potently inh...