复发性流产(RSA)在我国发病率呈上升趋势,由免疫功能紊乱导致局部凝血功能异常渐受重视。研究证实抗心磷脂抗体（ACA）可激活血管内皮细胞TLR-4/NF-κB通道，引起母胎界面局部微血栓形成，导致胎盘低灌注与胚胎停育，但机制尚不清楚。课题组前期研究发现补肾活血法经验方丹寿汤能有效治疗ACA阳性者的自然流产，降低ACA阳性孕鼠胎盘组织PAF及VEGF mRNA表达，提出“丹寿汤可能有拮抗内皮细胞损伤，抑制局部血栓形成”假说。通过建立ACA致妊娠丢失孕鼠模型，采用细胞培养、Western-blot 及RT-PCR等技术，观察丹寿汤干预后内皮细胞信号通路TLR-4、NF-κB的启动子DNA甲基化水平，粘附分子ICAM-1、VCAM-1及 TF、 IL-6、TNFα等蛋白及mRNA的表达水平，揭示丹寿汤对内皮细胞的抗凝调控机制，探索补肾活血法治疗RSA新的靶点与途径。

Recurrent spontaneous abortion (RSA) is a reproductive problem with poorly understood etiology and shown an upward trend in Chinese. It is multifactorial in nature, and several factors are proposed to contribute to its pathogenesis. The coagulation abnormalities caused by autoimmune disorders are gradually being paid attention to RSA. Anticardiolipin antibody (ACA) is a kind of autoimmune antibody. Previous researches have showed that it could cause placental thrombosis and infarction, resulting hypoperfusion of placenta and fetal ischemia and hypoxia. But the mechanism is not clear enough. Our previous clinical studies have demonstrated that DanShou Tang, an experienced prescription of BuShenHuoXue Method could effectively treat ACA induced early threatened abortion and inhibit embryo resorption in ACA induced fetal loss models, down regulate mRNA expression of PAF and VEGF. Based on that, we hypothesize that BuShenHuoXue Method may potentially inhibit the vascular endothelial cell injury and inhibit the formation of local thrombosis. Through the establishment of ACA induced fetal loss pregnant rat model and vascular endothelial cell culture in vitro, we measure the methylation and histone acetylation levels of promoter DNA of vascular endothelial cell signal transduction pathway TLR-4 , NF- kappa B, mRNA and protein expression of downstream cytokines including ICAM-1, VCAM-1, TF and IL-6 and endothelial cell apoptosis after a DanShou Tang intervention, aiming to confirm the hypothesis and explore a new target and method for the drug treatment of RSA.