成纤维细胞中雌激素调控的Aquaporin 2与女性压力性尿失禁发病机制的研究

项目名称： 成纤维细胞中雌激素调控的Aquaporin 2与女性压力性尿失禁发病机制的研究

项目编号： No.81200429

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 谢臻蔚

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 压力性尿失禁（SUI）是严重影响中老年妇女生活质量的常见病，随着经济发展和人口老龄化，该病已引起整个医学界的重视。绝经是其发病的高危因素之一，但确切机制不清。多数学者认为，绝经后雌激素低下引起的尿道支撑组织细胞外基质（ECM）重构障碍可导致SUI发生，而ECM重构由成纤维细胞迁移、功能活化来主导。水通道蛋白（AQPs）与细胞迁移、创伤修复密切相关。在前期研究中，我们课题组已证实雌激素直接调控水通道蛋白2（AQP2）的表达，并首次发现女性尿道支撑组织成纤维细胞中存在AQP2，其表达下降与雌激素低下和SUI发病密切相关，但其调控机制不明。本项目拟通过临床实验和体外细胞实验，以研究成纤维细胞功能为切入点，采用AQP2过表达和干扰技术，阐明尿道支撑组织成纤维细胞AQP2表达对细胞迁移、增殖和ECM合成分泌功能的调控及机制。本课题将有望从新的视觉阐述SUI发病机制，并为SUI早期防治提供科学依据。

中文关键词： 水通道蛋白2；成纤维细胞；压力性尿失禁；细胞外基质；雌激素

英文摘要： With the advent of aging society and the pursuit of the high quality of life, female stress urinary incontinence (SUI), as a common chronic disease of women, is attracting more and more attention. Although SUI has been shown to increase with age and is often associated with menopause, the delicate mechanism of SUI induced by estrogen deficiency following menopause is still unclear. Extensive research has demonstrated abnormal extracellular matrix (ECM) remodeling of female periurethral connective tissues, which could be induced by estrogen deficiency following menopause, may play a critical role of the pathogenesis of SUI.And the ECM remodeling is mainly induced by the activities of fibroblast (migration, proliferation, synthesis and secretion of collagen, etc.). It is now evident that aquaporins (AQPs) are closely related to the process of cell migration and wound healing, and our previous studies have revealed that estrogen could directly regulate the AQP2 expression. We also found the expression of AQP2 in fibroblasts of female periurethral connective tissues from postmenopausal patients significantly decreased compared with that in premenopausal patients. However, the regulation mechanism is unclear. We believe that AQP2 may be involved in the pathogenesis of SUI induced by estrogen deficiency.This project

英文关键词： Aquaporin-2；Stress urinary incontinence；Extracellular matrix；Fibroblasts；estrogen