基于miR-199a介导的NF-κB通路研究益气活血方抑制内异症子宫内膜干细胞黏附侵袭的作用机制

Endometriosis (EMs) is a major research topic in the field of gynecology, of which the recurrence rate are very high. However, its pathogenesis is not clear so far. Yiqihuoxue Recipe is an effective experience prescription for the treatment of EMs， previous studies have found Yiqihuoxue Recipe can inhibit endometrial adhesion and invasion ability and regulate NF-κB，which can prevent and treat recurrent endometriosis. Endometrial stem cells (EnSCs) with a high degree of adhesion and invasion ability is the key to recurrence of EMs.It was found that miR-199a can inhibit the proliferation and migration of EnSCs, and can inhibit endometrial adhesion and invasion ability through NF-κB signaling pathway,which play a key role in pathogenesis of endometriosis.Thus we propose a hypothesis:“Yiqihuoxue Recipe inhibits the EnSCs adhesion and invasion ability by the way of regulating miR-199a-mediated NF-κB signaling pathway”..In this study, we plan to establish the EMs rat models and endometrial stem cells, observe the endometrial adhesion and invasion ability and the key index of the miR-199a-mediated NF-κB signaling pathway.Then,we can found out research the mechanism of Yiqihuoxue Recipe preventing and treating recurrent endometriosis,and elucidate the key target of Yiqihuoxue Recipe inhibiting EnSCs adhesion and invasion ability.

子宫内膜异位症（EMs）复发率高且发病机制不明，是妇科领域重大研究课题。益气活血(YQHX)方是治疗EMs的有效经验方，前期研究证实YQHX方能抑制子宫内膜的黏附侵袭能力并对NF-κB分子有调控作用从而防治EMs复发。子宫内膜干细胞(EnSCs)高度的黏附侵袭能力是EMs复发的关键，研究发现miR-199a能抑制子宫内膜干细胞的增殖及迁移性，且能通过调控NF-κB信号通路抑制子宫内膜的黏附侵袭能力，是EMs发生发展的重要机制。由此提出“YQHX方通过调控miR-199a介导的NF-κB通路抑制子宫内膜干细胞的黏附侵袭能力，从而防治EMs复发”的科学假说。.本研究拟建立大鼠EMs模型及原代培养人子宫内膜干细胞，对子宫内膜干细胞的黏附侵袭能力及miR-199a介导的NF-κB信号通路的关键指标进行观察，探索YQHX方防治EMs复发的机制，阐明YQHX方抑制子宫内膜干细胞黏附侵袭的关键靶点。

子宫内膜异位症（endometriosis，EMs，简称内异症）是妇科领域常见病、疑难病。内异灶病变广泛、形态多样，虽为良性疾病，但具有明显的侵袭、转移、复发等恶性生物学行为，严重影响了妇女的健康和生活质量。因此临床迫切需要副作用小、可长期服用、有效治疗EMs的新药。本课题组长期致力于中医药治疗EMs的探索，益气活血（YQHX）方源于上海市名中医齐聪教授防治 EMs 复发的经验方，临床疗效确切。本研究基于miR-199a介导的NF-κB通路探讨益气活血治疗子宫内膜异位症机制研究。.结果表明:1）YQHX方能缓解EMs术后复发患者临床症状，缩小卵巢囊肿，下调血清CA125值，降低复发率，并能改善患者的免疫功能，且安全性好，不良反应较少， 具有较广的应用前景。2）内异症异位灶组织存在独特的表观印迹，miRNA可能是EMs的发生发展机制之一，影响的基因及信号通路（炎症相关通路、自噬相关通路、黏附—侵袭—血管生成相关通路等），本研究又从另一角度又探讨了miRNA抑制子宫内膜异位症患者的自噬，抑制子宫内膜基质细胞的增殖和侵袭，可以作为我们后续研究YQHX方作用机制的切入点。3）YQHX方可以有效抑制内异灶中NF-κB的表达，抑制NF-κB相关信号通路的启动，多靶点、整体改善盆腔微环境，有效抑制子宫内膜的黏附侵袭，从而治疗EMs。4）YQHX方具有抗子宫内膜干细胞黏附侵袭的药理学效应，其机制部分是通过调控miR-199a介导NF-κB 通路信号通路发挥作用。