基于E2-巨噬细胞-PGE2通路研究清热化瘀法治疗子宫内膜异位症的机制

子宫内膜异位症（EMs）是临床常见的难治性妇科疾病，我们在临床实践中发现，清热化瘀法对瘀热型EMs的疗效确切，但存在个体差异。有研究证实，EMs病灶微环境中巨噬细胞的选择性活化参与了EMs病理过程，而雌激素信号途径参与调控巨噬细胞的选择性活化。我们在前期研究中发现，清热化瘀法能下调EMs大鼠血清E2水平，并能影响异位病灶中巨噬细胞极化相关信号通路的活性。我们由此推测：清热化瘀法可能通过调节E2介导的巨噬细胞选择性活化，改变腹腔内炎症和血管生成相关因子的水平，抑制局部炎性反应和血管生成过程，进而抑制异位子宫内膜的侵入和生长。为此，本项目拟利用人异位子宫内膜间质细胞和巨噬细胞模型、EMs大鼠模型，以及清热化瘀方治疗EMs患者队列，从分子、细胞、动物和人体等多个层面，探讨清热化瘀法治疗EMs的药理学机制，寻找可用于预测其疗效的潜在生物标志物，为清热化瘀法的优化和个体化诊疗技术的发展提供理论依据。

We confirmed that Clearing heat and removing blood stasis therapy was a clinical effective treatment for endometriosis. Studying on EMs with rat models of autologous transplantation, we found that Clearing heat and removing blood stasis therapy can reduce serum E2 level and various inflammatory factors in peritoneal fluid, and cause many changes in signal pathways associated with macrophage polarization in ectopic lesions. To elaborate on the key cytological mechanism, we hypothesized that Clearing heat and removing blood stasis therapy, through a number of targets on specific cells, modulates the secretory function of macrophages induced by E2, inhibits the secretion of PGE2 and other inflammatory factors by macrophages, and further reduces the inflammatory response in the EMs lesions, improves abdominal inflammatory microenvironment of EMs, and consequently inhibits the growth of ectopic endometrial stromal cells. As a continuous subject program, the aim of this project is to discover different cellular targets of Clearing heat and removing blood stasis therapy through in vivo animal experiments and in vitro cell experiments, and to clarify the modern biological significance of TCM treatment principles. On the basis of defining its targets of cytology, we proposed that the E2-macrophage-PGE2 feedback regulation was the key mechanism for the pathogenesis of EMs, in order to improve the EMs TCM diagnosis and treatment of EMs and to discover the new target of EMs clinical diagnosis, and create a new clinical technology.