PrPc通过加强ESC自身生存能力及抑制巨噬细胞吞噬功能以促进子宫内膜异位症进展的机制研究

子宫内膜异位症（EMS）是难根治、易复发的常见病，病灶形成有赖于优良的“种子”-子宫内膜基质细胞（ESC）及局部异常免疫微环境。前期研究显示，雌激素可促进ESC内朊蛋白（PrPC）表达，且PrPC能促进ESC的生存、胆固醇的合成及抑制巨噬细胞的吞噬功能，PRNP基因（PrPC编码基因）敲除及过表达小鼠EMS模型证实，PrPC可显著促进EMS的进展，但其机制尚不明确。因此，我们假设：EMS异位灶局部高雌激素水平促进了ESC内PrPC的表达，异常表达的PrPC一方面通过改变细胞代谢模式与雌激素的合成促进ESC自身生存，另一方面以外泌体的形式被巨噬细胞摄取，抑制其吞噬功能，共同促进EMS的进展。本课题以体外实验模拟盆腹腔微环境及动物体内实验验证其分子机制为研究手段，研究EMS中PrPC调控ESC生存能力及巨噬细胞吞噬功能的病理机制，旨在为EMS发病机理的研究提供新思路。

Endometriosis (EMS) is a common debilitating gynecological disease. Formation of endometriosis lesion highly depends upon the implantation of endometrial stromal cells（ESC）and immune tolerance of local microenvironment. Previous study of our group suggested that Prion protein (PrPC) could significantly increase the cell viability, cholesterol synthesis of ESC and inhibit macrophage phagocytosis in vitro at the same time; rodent EMS models of PRNP gene（PrPC coding gene) knockout and over-expressing mice confirmed that PrPC contributed to the progression of EMS in vivo. While the underlying molecular mechanism remains to be elucidated. Hereby, we hypothesize: 1 Hyperestrogenic environment could increase the expression of PrPC in ESC; 2 Overexpression of PrPC might contribute to the aberrant viability of ectopic ESC. 3 PrPC is likely to be engulfed by macrophages in form of exosomes and inhibits their phagocytosis ability, thereby promote the progression of EMS. Our study recruits in vivo and in vitro model to mimic the pelvic microenvironment to investigate the expression and regulatory factors of PrPC of ESC in EMS. This project might shed light on the role of PrPC in the pathogenesis of endometriosis with hope of providing new strategies in the combat against EMS.