膀胱过度活动症（OAB）发病率高，严重影响患者的生活质量，阐明其发生机制具有重大的社会意义。前期的青年基金项目研究发现脑源性神经营养因子（BDNF）调控BK通道在OAB的发生发展中发挥着关键作用，同时还发现该过程中伴随着血清反应因子（SRF）信号通路的激活。SRF是一类转录因子超家族成员，调节许多即早基因的活性，通过结合反式作用启动子序列CArG盒来调控逼尿肌基因表达，从而参与细胞周期调控，凋亡，生长和分化。既往研究和预实验结果证实BDNF具有调控SRF表达和活性的重要功能，Ras-MEK-ERK可能是这一调控机制的重要通路，因此这可能是OAB发生发展的又一潜在机制。本项目拟在前期基础上，在分子、细胞和动物水平检测过表达和干预SRF后，OAB发生和发展变化，以进一步探讨BDNF结合受体TrkB调控逼尿肌细胞SRF活性激活逼尿肌细胞收缩相关蛋白导致OAB进展的相关机制，为临床治疗提供新靶点。

The incidence of overactive bladder disorder (OAB) is very high, which seriously affects the quality of life of patients. It is of great social significance to elucidate its mechanism behind OAB. In the research of NSFC funding (81600588), we found that BDNF plays a key role in the regulation of BK channel in the development of OAB. During the investigation of BDNF regulate detrusor excitability, we also found the activation of serum response factor (SRF) signaling pathways. SRF, a member of a superfamily of transcription factors, regulates the activity of many early genes which can activate detrusor gene expression by combining the transactivator sequence CArG participating in cell cycle regulation, apoptosis, growth and differentiation. Previous studies and preliminary experimental confirmed that BDNF plays an important role in the regulation of SRF expression in which Ras-MEK-ERK may be an important pathway in the process, so the regulation may demonstrate another potential mechanism for the development of OAB. Current project intends to detect OAB development during overexpression and intervention of SRF at the molecular, cellular and animal levels in order to further explore the effect of BDNF binding receptor TrkB on the SRF activity of detrusor cells and activate downstream detrusor myocytes contraction-related protein function.