目的:观察复方丹参滴丸与硫酸氢氯吡格雷片抗血小板聚集的协同作用。方法:SD大鼠40只,随机分为4组,即空白对照组(灌胃等体积CMC-Na)、氯吡格雷组(灌胃氯吡格雷30 mg/kg)、复方丹参滴丸单独组(灌胃复方丹参滴丸324 mg/kg)和联合用药组(灌胃氯吡格雷30 mg/kg和复方丹参滴丸324 mg/kg),每组10只,雌雄各半,连续给药21 d,观察各组大鼠动-静脉旁路模型血栓形成的抑制效应;另取大鼠40只,给药后大鼠腹主动脉取血,测定各组间凝血四项参数;最后采用同源模建方法构建血小板聚集靶点P2Y12三维结构,进行模型验证和评价,研究复方丹参滴丸活性组分、氯吡格雷活性硫醇代谢物与靶酶间结合效应,多角度考察两种药物的抗血小板聚集协同增效。结果:除空白对照组外,其余各组均可在一定程度上抑制大鼠动-静脉混合血栓形成,延长出血时间,降低纤维蛋白酶原含量,合用组较单独用药组的上述作用增强,但差异无统计学意义;分子对接结果显示以MesATP为参照阈值(对接得分-5.150),复方丹参滴丸共有20个活性组分在阈值以上。结论:复方丹参滴丸能在一定程度上增强氯吡格雷抗大鼠血小板聚集,延长出血时间,降低纤维蛋白酶原、延长凝血时间,两种药物合用时体现出较好的抗凝血协同效应。
Objective: To study the synergistic action of Compound Danshen Dripping Pill(CDDP) on Clopidogrel Bisulfate(CPG)counteracting platelet aggregation. Methods: 40 Sprague-Dawley(SD) rats were randomized into four groups: normal control group(CMCNa),CPG alone group(30 mg/kg),CDDP alone group(324 mg/kg),co-administration group(CPG 30 mg/kg and CDDP 324 mg/kg).The rats received gastric infusion of corresponding drugs for 21 continuous days. Blood sample of SD rats were collected by puncture of the abdominal artery for the determination of coagulation parameters such as prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB) concentration and thrombin time(TT) in each group. Another 40 SD rats were used for the observation of inhibitory effect on the thrombosis in arteriovenous shunt. Finally,homology modeling and molecular docking were employed to simulate their interaction between the P2Y purinoceptor 12(P2Y12) target and bioactive compounds contained in CDDP. Results: The bleeding time of coagulation parameters was prolonged,the thrombosis in arteriovenous shunt was inhibited in the medication group. The above effect was much better in the combination group. The molecular docking showed that bioactive compounds contained in CDDP was able to inhibit target P2Y12. Conclusion: CDDP can enhance the effect of CPG on inhibiting platelet aggregation.