适配子Let7binhibitor-PS通过GPIb抑制血小板活化及抗栓机制研究

动脉血栓是致死性心血管疾病之源，传统抗血小板药物的临床获益可能正被出血风险的增加所抵消。随着对正常止血过程和病理性血栓形成机制差异认识的深入，GPIb可作为新型抗血小板药物的潜在作用靶点。新发现的基于核酸适配子理论的新一代抗栓药物靶点均为凝血因子，国内外尚无针对血小板表面功能受体的适配子出现。我们前期研究显示Let7binhibitor-PS以浓度依赖形式抑制凝血酶、瑞斯托霉素诱导的血小板活化聚集。由于两者可共同作用于GPIb，因此推测Let7binhibitor-PS可通过GPIb抑制动脉血栓形成。本项目拟进一步研究Let7binhibitor-PS与GPIb的相互作用；建立小鼠动脉血栓模型，验证Let7binhibitor-PS的抗栓作用及出血风险；同时通过小鼠心梗模型，明确Let7binhibitor-PS对心梗预后的改善，以开发抗血小板的核酸适配子新药。

Arterial thrombosis is a source of fatal cardiovascular disease, and the potential benefits of traditional antiplatelet drugs may be offset by an increased risk of bleeding. With the in-depth understanding of the differences between normal hemostatic process and pathological thrombosis, GPIb can be used as a potential target of new antiplatelet drugs. The newly discovered new generation of antithrombotic drugs based on nucleic acid aptamer theory all target coagulation factors, and there are no aptamers for functional receptors on platelet surface at home and abroad. Our previous studies showed that Let7b inhibitor-PS inhibited platelet activation and aggregation induced by thrombin and ristocetin in a concentration-dependent manner. Since both of them can act on GPIb, it is speculated that Let7b inhibitor-PS can inhibit arterial thrombosis through GPIb. The purpose of this project is to further verify the interaction between Let7b inhibitor-PS and GPIb; to establish a mouse arterial thrombosis model to determine the antithrombotic effect of Let7b inhibitor-PS and the risk of bleeding; at the same time, through the mouse myocardial infarction model, to confirm the improvement of Let7b inhibitor-PS on the prognosis of myocardial infarction, in order to develop new antiplatelet nucleic acid aptamers.