腹腔巨噬细胞分泌的exosome在子宫内膜异位症发生及疼痛机制中的作用研究

Patients with endometriosis (EMs) suffer from abdominal immune disorders, in which peritoneal macrophage (pMφ) plays a key role. Existing literatures and our preliminary work confirmed that activated pMφ could secrete inflammatory substances such as TNF-α, IL-1β, IL-6 and VEGF, which could promote the proliferation and adhesion of ectopic endometrial cells, facilitate angiogenesis of ectopic focuses and participate in the down regulation of pain threshold. Recent studies revealed that the exosome from pMφ containing proteins and microRNAs participated in intercellular regulation, still lacking the knowledge of the molecular types contained in exosome, the target cells of exosome and the effect of exosome on EMs. This project intends to separate exosome from pMφ of all different stages of Ems and analyze inner proteins and microRNAs, then identify its target cells and downstream regulatory pathways. After that, we will study the effects of exosome from pMφ and its inner microRNA on the occurrence, adhesion, angiogenesis, development of nerve fibers and pain threshold of endometriosis by raising and suppressing related microRNAs. These studies can provide new ideas and methods for the research of molecular mechanisms and the treatment of EMs.

子宫内膜异位症（EMs）患者存在腹腔局部免疫紊乱，其中腹腔巨噬细胞(pMφ)在EMs发生进程中发挥关键作用。已有文献和我们前期工作证实，活化的pMφ分泌的TNF-α、IL-1β、IL-6和VEGF等炎性物质，能促进异位内膜细胞的增殖、粘附以及新生血管生成，并参与了疼痛阈值的下调。近年发现pMφ分泌的exosome内含蛋白和微小RNA，发挥了胞间调控的作用，但exosome内含物质种类、靶细胞及在EMs中的作用机制国内外尚未见报道。本项目拟分离不同期别EMs患者腹腔中pMφ，对其分泌exosome包含的miRNA和蛋白质进行测序鉴定与功能分析，同时对其靶细胞和下游调控通路进行分析；建立大鼠EMs模型，局部上调或抑制相关miRNA表达，研究exosome及其内含miRNA种类对EMs发生、粘附、血管发生、神经纤维生长和疼痛阈值的影响。本研究可为EMs发生的分子机制研究和治疗提供新的思路和靶点。

子宫内膜异位症（EMs）患者存在腹腔局部免疫紊乱，其中腹腔巨噬细胞(pMφ)在EMs发生进程中发挥关键作用。已有文献和我们前期工作证实，活化的pMφ分泌的TNF-α、IL-1β、IL-6和VEGF等炎性物质，能促进异位内膜细胞的增殖、粘附以及新生血管生成，并参与了疼痛阈值的下调。近年发现pMφ分泌的exosome内含蛋白和微小RNA，发挥了胞间调控的作用，但exosome内含物质种类、靶细胞及在EMs中的作用机制国内外尚未见报道。本项目通过分离不同期别EMs患者腹腔中pMφ，对其分泌exosome包含的miRNA和蛋白质进行测序鉴定与功能分析，同时对其靶细胞和下游调控通路进行分析；建立大鼠EMs模型，局部上调或抑制相关miRNA表达，研究exosome及其内miRNA种类对EMs发生、粘附、血管发生、神经纤维生长和疼痛阈值的影响。本研究为EMs发生的分子机制研究和治疗提供了新的思路和靶点。