女性压力性尿失禁(SUI)和盆腔器官脱垂(POP)是因盆底支持组织松弛引起的盆底功能障碍性疾病（PFD），其发病机制尚未完全阐明。我们的前期研究证实氧化应激（OS）在妊娠、分娩等机械力损伤所致POP发病中发挥关键作用。核因子E2相关因子2（Nrf2）是调节细胞抗氧化系统的关键蛋白之一，参与调控OS，但目前尚无Nrf2对SUI的作用及机制的研究。根据前期预实验结果，本项目拟应用野生型、Nrf2基因敲除小鼠构建机械力诱导的SUI动物模型，观察盆底支持组织如阴道前壁细胞外基质表型变化，同时检测尿动力学相关指标如漏尿点压力(LPP)、腹部漏尿点压力（ALPP)、最大尿道关闭压(MUCP)的改变,并结合敲除和过表达Nrf2基因乳鼠的阴道前壁成纤维细胞离体机械力损伤模型进行验证，深入探讨由Nrf2介导的相关信号通路，以期阐明Nrf2对SUI的作用及具体机制，为SUI的防治提供理论基础和临床治疗靶点。

Pelvic floor dysfunction (PFD) including stress urinary incontinence (SUI) and pelvic organ prolapse (POP) is caused by relaxation of the pelvic floor supporting tissues, of which the pathogenesis is unknown. Our previous studies have confirmed that oxidative stress (OS) play a key role in the process of POP induced by mechanical strain injuries from pregnancy and childbirth. Nuclear factor-E2-related factor 2（Nrf2） is one of the key regulators in cellular antioxidant defense system, involved in the regulation of oxidative stress, but there is no specific study examining the mechanisms underlying the effect of Nrf2 on SUI. Our project plans to establish an experimental animal model of mechanical-strain-induced SUI with Nrf2-gene-knockout and wild type mouse, so as to observe the microstructure changes in extracellular matrix (ECM) in anterior vaginal wall and other phenotypic changes. In vivo changes of relevant urodynamic indicators, including point pressure (LPP), abdominal leak point pressure (ALPP) and maximum urethral closure pressure (MUCP) were also observed. Combining with in vitro cell model of fibroblasts derived from anterior vaginal tissue of neonatal mouse with genetic knockout or overexpression of Nrf2, we are able to thoroughly investigate Nrf2-mediated signaling pathways. Our project helps to elucidate the role of Nrf2 in SUI pathogenesis and the underlying mechanism, and provide theoretical basis and clinical therapeutic target for the prevention and treatment of SUI.