ERβ调控H2S通路在膀胱高敏感及女性间质性膀胱炎/膀胱疼痛综合症发生发展中的作用和机制研究

女性IC/BPS表现为膀胱敏感性增高的一系列症状，发病机制主要包括尿路上皮感觉功能改变、自身免疫异常及炎症刺激等。女性IC/BPS与雌激素轴的改变密切相关，ERβ通路在IC/BPS的发病中发挥重要作用。前期构建的尿路上皮特异性ERβ转基因小鼠膀胱中H2S通路发生改变。而H2S在平滑肌舒张、疼痛感觉、炎症反应等多个生理过程中发挥作用。H2S可在泌尿生殖道中发挥作用，但在IC/BPS中尚未有系统研究。因此提出ERβ通过调控H2S通路参与膀胱高敏感及女性IC/BPS 的发生与进展这一假设。为验证这一假设，本项目拟采用多种动物模型及临床IC/BPS患者标本，从三个方面开展：①探究IC/BPS患者中ERβ及H2S分子通路变化情况，建立IC/BPS患者预测模型；②探讨ERβ对H2S的调节作用；③探究ERβ调控H2S通路对膀胱敏感性和IC/BPS的影响。为女性IC/BPS的防治提供理论基础及作用靶点。

Female IC/BPS patients manifest with a series of symptoms of hypersensitive bladder. The mechanism of IC/BPS consists of the changes of urothelial sensory function, abnormal autoimmune reaction, inflammatory stimulation and so on. The pathogenesis of female IC/BPS is closely related to the changes of estrogen axis and ERβ pathway plays an important role in the pathogenesis of IC/BPS. Previous study indicated the changes of H2S pathways in urothelial ERβ-specific transgenic mice bladder. The H2S pathways have an influence on a number of physiological processes such as smooth muscle relaxation, pain sensation, inflammation and so on. Besides, The H2S pathways play a role in the urogenital tract. However, H2S pathways have not been systematically studied in IC/BPS. Therefore, we propose that ERβ regulating H2S pathway played an important role in hypersensitive bladder and female IC/BPS. To verify this hypothesis, we intends to use a variety of animal models and clinical IC/BPS patients samples from three aspects. Firstly, the changes of ERβand H2S molecular pathways will be examined in IC/BPS patients and the predictive models will be establish. Next, we intend to explore the regulating effect of ERβto H2S. Last but not the least, the influence of ERβregulating H2S pathway to hypersensitive bladder and female IC/BPS will be further investigate. We would like to provide the theoretical basis and targets for female IC/BPS patients.