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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 observe the synergistic effect of compound Danshen dripping pills and clopidogrel bisulfate against platelet aggregation. Methods: Forty Sprague-Dawley rats were randomly divided into 4 groups: blank control group (intragastric administration of equal volume of CMC-Na), clopidogrel group (intragastric administration of clopidogrel 30 mg / kg) (Intragastric administration of compound Danshen dripping pills 324 mg / kg) and combination group (intragastric administration of clopidogrel 30 mg / kg and compound Danshen dripping pills 324 mg / kg), each group 10, male and female, continuous administration 21 d, to observe the inhibitory effect of thrombosis in the animal model of arterio-venous bypass in each group; another 40 rats were taken from the abdominal aorta of the rats after administration, and the four parameters of coagulation were determined; Modeling construction of platelet aggregation target P2Y12 three-dimensional structure, model validation and evaluation of the compound Danshen dripping pills, clopidogrel active thiol metabolites and target enzyme binding between the multi-angle study of the two anti-drug Platelet aggregation Synergy. Results: Except for the blank control group, all the other groups could inhibit the arteriovenous thrombosis, prolong the bleeding time and reduce the content of fibrinogen in the combined groups, but the difference was significant No statistical significance; molecular docking results show MesATP as a reference threshold (docking score -5.150), compound Danshen dripping pills a total of 20 active components above the threshold. CONCLUSION: Compound Danshen Dripping Pills can enhance the platelet aggregation of clopidogrel to a certain extent, prolong the bleeding time, reduce the fibrinogen and prolong the clotting time. The synergistic effect of anticoagulant when the two drugs are combined is obvious.