女性压力性尿失禁（SUI）严重损害女性生活质量，盆底电刺激（PES）治疗能有效防治 SUI，但机制尚未明确。我们前期研究证实盆底支持结构细胞外基质（ECM）重构是SUI的重要发病机制，电刺激可通过TGFβ1-Smad2/3通路调控ECM的代谢和重构。本项目拟采用野生型小鼠、Cav3.2基因敲除小鼠和整合素β1基因敲除小鼠构建SUI模型和PES小鼠模型并进行评估，将各组小鼠阴道前壁组织进行原代成纤维细胞培养，建立细胞电刺激模型，采用分子生物学技术、电生理学方法，结合激光共聚焦成像、实时扫描技术等细胞生物学方法，旨在整体、组织和细胞水平探讨Ca2+、calpain-talin、整合素β1及TGFβ1-Smad2/3信号通路调控ECM代谢与重构的过程，阐明PES治疗SUI的机制，并探索以整合素β1为靶点的SUI治疗途径，为临床SUI的防治提供依据。

Female stress urinary incontinence (SUI) affects women's quality of life severely. Pelvic electrical stimulation (PES) has been applied to prevent and improve symptoms of SUI in clinic for decades. However, the mechanism has not been elucidated. Our previous studies have found that extracellular matrix remodeling may be the pathogenesis of SUI. In addition, electrical stimulation (ES) could regulate metabolism and remodeling of extracellular matrix through TGF β1-Smad2/3 signaling pathway. Our project plans to develop a SUI murine model and an ES therapy murine model by using wild-type, Cav 3.2 gene knockout and integrin β1 gene knockout mice, and then evaluate these models. The fibroblasts will be primary cultured from the vaginal anterior tissue of the mice, and an ES cell model will be developed thereof. Molecular biological technology, electro- physiological method, and cell biology techniques, such as confocal scanning laser microscopy and real time scanning technique will be used to explore the function of Ca2+, calpain-talin, integrin β1, and TGF β1-Smad2/3 signaling pathway in the regulatory of extracellular matrix metabolism and remodeling at the integral, tissue and cell level, respectively. Our project will provide knowledge for the mechanism and relevant signaling pathways underlying PES treatment of SUI, and provide further evidence for integrin β1 as a novel therapeutic target for the clinical prevention and treatment of SUI.