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目的探讨丹参素(Danshensu,DSS)抗血小板聚集的分子作用机理及其可能的作用靶点,为丹参素及含有丹参素的中药在临床心脑血管疾病的防治提供科学依据。方法用凝血酶(thrombin)诱导血小板聚集,用血小板聚集仪检测丹参素对血小板聚集率的影响;采用免疫共沉淀的方法,研究丹参素对血小板蛋白质二硫键异构酶ERp57和整合素αⅡbβ3的相互作用;用反向分子对接服务器PharmMapper预测丹参素抗血小板聚集的相关作用靶点;用MOE-Dock的方法,对反向对接的结果进行验证。结果 10μmol·L~(-1)和100μmol·L~(-1)丹参素显著抑制凝血酶诱导的血小板聚集,并呈时间剂量依赖关系(P<0.05)。丹参素抑制血小板ERp57和αⅡbβ3蛋白质的相互作用,凝血因子7(Coagulation factor Ⅶ)可能是其作用靶点之一。结论丹参素具有抗凝血酶诱导血小板聚集的作用,其作用机制与调控血小板ERp57和αⅡbβ3蛋白质的相互作用,以及凝血因子7有关。
Objective To explore the molecular mechanism of anti-platelet aggregation of Danshensu (DSS) and its possible target of action, and to provide a scientific basis for the prevention and treatment of clinical cardiovascular and cerebrovascular diseases by Danshensu and Chinese traditional medicine containing Danshensu. Methods Thrombin (thrombin) was used to induce platelet aggregation. The effect of danshensu on the rate of platelet aggregation was detected by platelet aggregation assay. The effect of danshensu on platelet protein disulfide isomerase ERp57 and integrin αⅡbβ3 Interaction; the use of reverse molecular docking server PharmMapper predict the anti-platelet aggregation of Danshensu related targets; MOE-Dock method, reverse docking results were verified. Results Danshensu (10 μmol·L -1) and 100 μmol·L -1 significantly inhibited thrombin - induced platelet aggregation in a dose - and time - dependent manner (P <0.05). Danshensu inhibits platelet ERp57 and αⅡbβ3 protein interactions, and coagulation factor 7 may be one of its targets. Conclusion Danshensu has antithrombin-induced platelet aggregation, and its mechanism of action is related to the regulation of platelet ERp57 and αⅡbβ3 protein interactions, as well as coagulation factor 7.