补肾活血方调控血小板/ATP/P2X7/细胞自噬通路干预aCL致复发性流产的作用机制

近年来，复发性流产（RSA）发病率逐渐上升，免疫功能紊乱导致局部血栓形成是关键致病环节，抗心磷脂抗体（aCL）是局部血栓形成的主要因素。本课题组前期研究发现补肾活血方-丹寿汤对RSA具有良好疗效，并可缓解aCL介导内皮细胞损伤、血小板活化、P2X7上调以及自噬的抑制。另外文献显示aCL-β2GP1可诱导局部血栓、激活血小板释放ATP，进一步作用于P2X7，抑制细胞自噬水平。依据文献报道与前期研究结果，推测丹寿汤可阻断aCL-β2GP1形成，抑制血小板释放ATP，从而缓解P2X7介导内皮细胞自噬抑制，防止局部血栓的形成。为此，我们拟借助aCL-RSA大鼠和细胞模型，利用分子生物学手段检测该过程中涉及的关键信号分子，并用慢病毒载体构建技术精准调节靶分子，明确丹寿汤经血小板调节内皮细胞生物学功能发挥治疗RSA的作用机理，为补肾活血法治疗RSA提供数据支持及理论依据。

In recent years, the incidence of recurrent abortion (RSA) has gradually increased. Local thrombosis caused by immune dysfunction is the key pathogenic link, and anti-cardiolipin antibody (ACL) is the main factor of local thrombosis. The previous research of our group found that Bushen Huoxue Formula-Danshou Decoction has a good therapeutic effect on RSA, and can significantly alleviate aCL-mediated endothelial cell damage, platelet activation, P2X7 up-regulation and autophagy inhibition. In addition, the literature shows that aCL-β2GP1 can induce local thrombosis and activate platelets to release ATP which can act on P2X7 to inhibit cell autophagy. According to literature reports and previous research results, it is speculated that Danshou Decoction can block the formation of aCL-β2GP1 and inhibit the release of ATP from platelets, thereby alleviating the P2X7-mediated endothelial cell autophagy inhibition and preventing the formation of local thrombus.To this end, we intend to use the rat and cell models of RSA, while utilizing molecular biology to detect key signaling molecules involved in this process, and applying the lentiviral vector construction technology to accurately regulate the target molecules so as to clarify the mechanism of Danshou Decoction in the treatment of RSA by regulating the biological function of endothelial cells through platelets, and to provide data support and theoretical basis for the treatment of RSA by tonifying kidney and promoting blood circulation.