HCK通过下调巨噬细胞功能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、易复发的妇科常见病。研究显示，盆腹腔局部免疫微环境异常，无法有效清除异位灶内膜间质细胞（ESC）反而促进其生长种植。随着疾病进展，巨噬细胞对ESC吞噬功能降低，而造血细胞激酶（HCK）是调节巨噬细胞功能的关键分子。目前HCK在内异症中的作用机制尚不明确。本课题组前期试验结果表明HCK基因敲除小鼠腹腔液中巨噬细胞吞噬功能显著下降，有鉴于此，我们推测局部微环境中激素、细胞因子可下调巨噬细胞的HCK，导致巨噬细胞代谢物异常，进而抑制巨噬细胞的吞噬功能，最终促进EMS进展。本课题以体外试验模拟盆腹腔微环境及动物实验为研究手段，研究EMS中巨噬细胞HCK水平及调控因素，探讨HCK通过改变巨噬细胞代谢的途径调控其吞噬功能的具体机制，进而解析HCK通过下调巨噬细胞吞噬功能来参与调节ESC生物学行为，促进EMS进展的病理机制。本课题将为EMS发病机理研究提供新的研究思路。

Endometriosis is a common, refractory and debilitating gynecological disorder. Accumulating evidence supported that aberrant immune milieu in peritoneal cavity of women with endometriosis might hinder the clearance of the endometriotic tissue. On the contrary, it promotes the growth and implantation of endometrial stromal cells (ESC). Hematopoietic cell kinase (HCK) is a key molecule regulating phagocytosis of macrophages. Meanwhile, its role in the pathogenesis of endometriosis remains to be elucidated. Our preliminary data suggested that the phagocytic activity of peritoneal macrophages in HCK knockout mice was compromised compare to wild type mice. Based upon those, we hypothesize that hormones, cytokines etc. of the micro-environment might down-regulate HCK expression and/or activity in macrophages, which in return might alter metabolite pathways of macrophages and inhibit its phagocytosis and ultimately promote the progression of endometriosis. Hence, we recruit both in vitro and in vivo models to investigate the expression and regulation of HCK of macrophages in endometriosis . We shall explore the specific metabolic mechanism of HCK down-regulate phagocytosis and the cross-talk between ESC and macrophages to promote the progression of endometriosis. This project might shed lights on the pathogenesis of endometriosis and provide new strategies in the combat against endometriosis.