膀胱过度活动症（OAB）是一种尿急综合征，发病率高，其发生机制尚未明确。大电导钙激活钾通道（BK）通过维持静息膜电位和偶发动作电位的初始去极化，引起膀胱逼尿肌阶段性的收缩导致膀胱兴奋异常，并且受脑源性神经营养因子（BDNF）的调控。本课题组前期研究发现BDNF在OAB患者中表达增加，从而引起膀胱感觉传入神经元的兴奋性异常。BDNF可以结合膀胱逼尿肌细胞上的肌球蛋白相关激酶（TrkB）受体，通过经典的Ras-MEK-ERK途径上调环一磷酸腺苷反应元件结合蛋白（CREB）的表达，同时CREB也证实与OAB的发生发展有密切关联。因此推测，BDNF-TrkB结合后可能通过诱导CREB的产生，下调BK通道表达活性参与OAB的发生。本研究拟在细胞水平上检测CREB的过表达和沉默与BK通道的电流活性改变之间的关系，以及探讨CREB在核酸水平调控BK通道蛋白的表达参与OAB发生机制中的作用机理。

Overactive bladder (OAB) is a kind of syndrome characterized by urgency urinates. Although high prevalence of OAB, the mechanism still need to clarify. Large conductance Ca2+-activated K+ channel (BK) trigger increased contractility of bladder detrusor by maintain initial resting membrane potential and action potential depolarization and was also innervated by brain-derived nerve factor (BDNF). Our research groups have already confirmed that BDNF expression increased in patients with OAB which can lead to abnormal excitatory of afferent fiber. BDNF combined with TrkB receptor and activated cAMP response element-binding protein (CREB) through classical Ras-MEK-ERK pathway. CREB also have been proved involve in the development of OAB. Therefore, we hypothesis that BDNF combined with tropomyisin-related kinase (TrK) receptors, released cAMP response element-binding protein (CREB), and then down-regulate the expression of BK channel, which can lead to occur of OAB. In current project, we aim to low and over expression of CREB, then observe the electric current of BK channel in the level of cell line model. We also want to know the mechanism of CREB regulate the expression of BK channel in gene level involve in the development mechanism of OAB.