自然流产（SA）是常见的孕育障碍，孕激素受体(PR)调控滋养细胞凋亡是SA重要的发病机制，课题组前期研究证实减味寿胎丸能提高流产孕鼠PR表达，抑制滋养细胞凋亡，增强黄体功能而维持妊娠；同时发现SA患者绒毛组织miR-126-3p表达显著上调，提示miR-126-3p在SA发病中的重要作用。通过生物信息软件预测与文献研究均提示PR为miR-126-3p调控靶基因，故提出假说：减味寿胎丸可能通过下调miRNA-126-3p从而上调PR表达，改善滋养细胞功能达到补肾安胎的作用。基于此，针对发生SA的重要病理环节，整合基因芯片、生物信息学、分子生物学方法，利用细胞和动物模型，希冀从整体-细胞-蛋白-基因水平阐明miRNA-126-3p调控PR表达作用机制，进而阐释减味寿胎丸治疗SA的具体分子机理，不仅为治疗SA提供新的药物靶点，亦丰富了"补肾安胎"的科学内涵。

Spontaneous abortion (SA) is a common breeding barrier. Deficiency of progesterone receptor (PR) causes trophoblast apoptosis and plays a pivotal role in the pathogenesis of SA. Our research team previously confirmed that Jian-Wei-Shou-Tai-Wan (JWSTW) increased PR expression, inhibited trophoblast apoptosis, ameliorated luteal function and maintained pregnancy. Our preliminary study also found that miR-126-3p also significantly increased in villi of patients with SA, suggesting that miR-126-3p is implicated in the pathogenesis of SA. Using Bio-info software, we predicted that PR is the downstream target gene of miR-126-3p. Our present hypothesis is that JWSTW decreases miR-126-3p and increases PR expression, ameliorating trophoblast function and preventing against SA. Thus, the present project aims to elucidate the molecular mechanism by which miR-126-3p regulates PR expression and uncovers the molecular mechanism by which JWSTW prevents against SA, using the methods of gene clip, bioinformation, molecular biology as well as in vivo and in vitro models. Our project would provide novel targets of drugs treated with SA and new insights on the therapy of reno-protection and Fetus stabilization.

流产是常见的生殖障碍，凋亡是其发生的关键环节。但是其具体法伤机制未知，基于前期研究正常早孕（要求人工流产）和胚胎停止发育患者组织miRNAS基因芯片筛选结果，进行了临床伦理审核，完成了扩大临床样本miRNA-126-3p的验证和临床指标的检测，筛选了miRNA-126-3p调控靶基因和同时进行了功能研究。分别构建了正常滋养细胞和米非司酮所致EVT细胞自然流产状态的细胞模型，研究了补肾安胎中药有效成分菟丝子总黄酮对其侵袭和迁移功能的影响。阐明了菟丝子总黄酮通过影响滋养细胞内MMP9调控其迁移和侵袭功能的安胎机制。首次验证了PR调控滋养细胞凋亡功能，并明确阐述补肾安胎中药有效成分川续断皂苷VI通过PR调控滋养细胞凋亡功能的机制，对于丰富SA发生机制有重要意义，同时也为筛选补肾安胎中药奠定良好的基础，构建的细胞模型为筛选流产药物机制研究提供了稳定的研究载体。