PSS与阿司匹林或氯吡格雷联合用药抗栓作用及机制

PROPYLENE GLYCOL ALGINATE SODIUM SULFATE COMBINED WITH ASPIRIN OR CLOPIDOGREL FOR THROMBUS PREVENTION AND ITS MECHANISM

目的探讨藻酸双酯钠(PSS)与阿司匹林或氯吡格雷联合用药对血栓形成影响及其作用机制。方法将70只雄性Wistar大鼠随机分为空白组、溶媒组(羟甲基纤维素钠)、PSS组、阿司匹林组、氯吡格雷组、PSS+阿司匹林组、PSS+氯吡格雷组。连续给药7d后,持续直流电刺激大鼠颈总动脉,记录各组大鼠血栓形成的时间;采用ELISA方法检测PSS组与空白组血清环氧合酶-1(COX-1)、环氧合酶-2(COX-2)及肝脏组织细胞色素P450酶亚型3A4(CYP3A4)的表达,Western blot方法检测血浆中凝血酶含量。结果 PSS组、氯吡格雷组、PSS+阿司匹林组、PSS+氯吡格雷组与空白组、溶媒组比较,PSS+阿司匹林组与阿司匹林组比较,PSS+氯吡格雷组与PSS组和氯吡格雷组比较,血栓形成时间均显著延长(F=19.61,P<0.05)。PSS组与空白组比较,血浆中凝血酶含量及被激活的凝血酶含量均下降(t=2.58、3.71,P<0.05),而两组血清COX-1、COX-2水平及肝脏组织CYP3A4表达差异均无显著性(P>0.05)。结论 PSS、氯吡格雷均有抑制血栓形成的作用,两者之间具有协同作用;PSS可能是通过抑制凝血酶活性来抑制血栓形成的。

Objective To assess the effect of propylene glycol alginate sodium sulfate（PSS）combined with Aspirin or clopidogrel on thrombus prevention and its mechanism. Methods Seventy male Wistar rats were divided into seven groups in random：blank group,solvent group（sodium cellulose glycolate）,PSS group,Aspirin group,clopidogrel group,PSS ＋ aspirin group,and PSS ＋ clopidogrel group.After seven days of successive medication,the carotid artery of the rats was continuously stimulated with direct current,the time of thrombosis recorded.Employing ELISA to detect the expressions of COX-1,COX-2in serum and CYP3A4 in liver of rats in the PSS group and the blank group,and Western blot was used to detect plasma thrombin.Results The thrombosis time in the PSS group,clopidogrel group,PSS＋ aspirin group,and PSS＋clopidogrel group were significantly prolonged compared with blank group and control group（F=19.61,P0.01）.Plasma thrombin and activated thrombin content were significantly decreased in PSS group as compared with the blank group（t=2.58,3.71;P0.05）,but the differences of levels of COX-1,COX-2,CYP3A4 in serum and in liver were not significant between the two groups（P0.05）. Conclusion Both PSS and clopidogrel have an action in inhibiting thrombosis,both of them show a synergistic effect.PSS is likely to play this action through inhibition of thrombin activity.