基于Let-7a miRNA探索补肾调血颗粒改善促排卵大鼠子宫内膜容受性的机制

子宫内膜容受性是决定胚胎能否顺利着床的关键因素。申请者前期研究发现“肾虚血瘀”是子宫内膜低容受性患者的主要中医证型，采用自主研制的补肾调血颗粒证实可有效改善促排卵患者子宫内膜容受性，并初步阐明雌激素受体 (ER)，孕酮受体 (PR) 参与了胚胎着床相关信号通路的调控，但更为详细的机制及药效物质对应作用尚不清晰。本课题拟从促排卵大鼠模型入手：①观察补肾调血颗粒对促排卵大鼠子宫微观形态以及子代安全性的影响；②利用高效液相色谱法对补肾调血颗粒的化学成分进行含量测定；③利用miRNA基因芯片技术，基因沉默技术深入探讨补肾调血颗粒是否通过抑制Let‐7a miRNA基因的过表达，增加ER、PR对下游容受性分子的调控。从而揭示补肾调血颗粒改善子宫内膜容受性的机理，阐明补肾调血颗粒提高辅助生殖成功率的科学内涵。

Endometrial receptivity is the key factor to determine whether the embryo can implant successfully. The previous study of the applicant found that "kidney deficiency and blood stasis" was the main TCM syndrome type in patients with low endometrial receptivity. Studies have demonstrated that the self-developed Bushen Tiaoxue granules can improve endometrial receptivity in ovulation patients, and clarified estrogen receptor (ER) and progesterone receptor (PR) are involved in the regulation of embryo implant-related signaling pathways but the mechanism of their action is still unclear. This project intends to start with the ovulation induction rat model: ① observe the effect of Bushen Tiaoxue granules on the uterine microscopic morphology and offspring safety of ovulation induction rats; ② high performance liquid chromatography (HPLC) was used to determine the chemical components of Bushen Tiaoxue granules. ③ using miRNA gene chip technology and gene silencing technology to further explore whether tonifying regulating blood granules can increase the regulation of ER and PR on downstream capacitivity molecules by inhibiting the overexpression of Let‐7a miRNA gene. This study reveals the mechanism of Bushen Tiaoxue granules to improve endometrial receptivity, and clarifies the scientific connotation of Bushen Tiaoxue granules to improve assisted reproductive success rate.