雌激素通过调节基质金属蛋白酶（MMP）影响阴道上皮屏障稳态在老年性阴道炎发病中的分子机制研究

老龄化问题目前是我国和世界面临的重大挑战，绝经后老年性阴道炎的发病率可以达50%以上，严重影响妇女的身心健康，每年消耗大量的医疗资源。雌激素缺乏是老年性阴道炎发生的核心环节，但是雌激素下降通过何种作用机制使阴道的上皮屏障功能受损目前尚不明确，国内外均缺乏相关的研究。我们的前期研究发现雌激素在阴道上皮中能下调脂多糖（LPS）诱导的MMPs升高和上皮钙粘蛋白（E-cad）降解，使阴道上皮细胞通透性的降低。本研究拟在此基础上，通过建立体内和体外模型，以雌激素通过MAPK和NF-κB信号通路对MMPs的代谢调节作为切入点，从细胞、动物模型及临床样本三个方面分层联合研究雌激素对阴道上皮MMPs的代谢调节及上皮屏障稳态失衡在老年性阴道炎发病过程中的作用及可能的分子机制。

The problem of aging is now a major challenge for our country and the world, the incidence of senile vaginitis can reach more than 50% after menopause, which seriously affects women's physical and mental health, and consumes a lot of medical resources every year. Estrogen deficiency is the key link in the pathogenesis of senile vaginitis. However, the effect of estrogen decline on the impairment of the epithelial barrier function of the vagina is still unclear, and there is no related research at home and abroad. Our previous studies found that estrogen can down regulate the MMPs increase and the E-cadherin degradation induced by lipopolysaccharide (LPS) in the vaginal epithelium, and decrease the permeability of vaginal epithelial cells. On this basis, We intend to establish in vivo and in vitro models, study the role of estrogen in the regulation of MMPs through the MAPK and NF-κB signaling pathways as a starting point, study the metabolic regulation of estrogen on MMPs in vaginal epithelium through the cell, animal model and clinical sample test, at the same time, we also study the role and possible molecular mechanism of the imbalance of the epithelial barrier homeostasis in the pathogenesis of senile vaginitis.