膀胱ICC中T型钙通道亚型变化在神经源性膀胱兴奋异常中的作用及机制研究

Neurogenic bladder（NB）is a is a high incidence of urinary system，with unsatisfactory clarified mechanism. Many researches of us and others have confirmed that detrusor instability with variated bladder excitation occupied its main mechanism，and there is an excitation regulation system relies in bladder, bridging the innervation and detrusor myocytes. With bladder ICC as its central, this excitation system can integrate impulses from the innervation, and transfer its integrated impulses to the target cells. T -type calcium channel of bladder ICC is an important channel of regulating the spontaneous excitation. However， NB had significant changes in spontaneous excitation control system. We assume that the variated T-type calcium isoforms originated excitation in bladder ICC might be the main reason for NB. In this study, based on our previous results, we will establish the rat NB model with spinal cord injury, and firstly investigate the express and function of T-type calcium channel isoforms in NB, combined with RNAi technology,living cells workstation and patch clamp techniques. Progressively, role of changes of T-type calcium channel isoforms in NB will be detected. The performation of this study might optically bring us new stratiges and targets for basic research and clinical treatment for NB.

神经源性膀胱（Neurogenic bladder, NB）是泌尿系统高发病，其膀胱功能障碍的机制尚不完全清楚。包括我们前期研究证实逼尿肌兴奋性异常所致膀胱功能障碍是其重要发生机制，且膀胱中存在桥接神经和逼尿肌细胞的自发性兴奋系统，这一系统以膀胱ICC细胞为枢纽，整合来自神经的信号，并传导至效应细胞。而T型钙通道是调控ICC细胞自发兴奋性的重要通道之一。研究还发现：NB中膀胱自发性兴奋调控系统发生显著改变。我们推测NB膀胱ICC细胞中T型钙通道亚型表达及功能的变化是自发性兴奋调控系统改变的重要机制。本研究拟在前期系统研究的基础上，构建脊髓损伤致NB大鼠模型，结合RNAi技术、活细胞工作站及膜片钳等技术，检测NB中ICC细胞T型钙通道亚型表达及功能的变化，并进一步探讨T型钙通道亚型的转变在NB发病中的作用及机制，为研究和治疗NB提供新的策略和靶点。

神经源性膀胱（Neurogenic bladder, NB）是泌尿系统高发病，其膀胱功能障碍的机制尚 不完全清楚。包括我们前期研究证实逼尿肌兴奋性异常所致膀胱功能障碍是其重要发生机 制，且膀胱中存在桥接神经和逼尿肌细胞的自发性兴奋系统，这一系统以膀胱ICC细胞为 枢纽，整合来自神经的信号，并传导至效应细胞。而T型钙通道是调控ICC细胞自发兴奋性 的重要通道之一。研究还发现：NB中膀胱自发性兴奋调控系统发生显著改变。我们推测NB 膀胱ICC细胞中T型钙通道亚型表达及功能的变化是自发性兴奋调控系统改变的重要机制。 本研究拟在前期系统研究的基础上，构建脊髓损伤致NB大鼠模型，结合RNAi技术、活细胞 工作站及膜片钳等技术，检测NB中ICC细胞T型钙通道亚型表达及功能的变化，并进一步探 讨T型钙通道亚型的转变在NB发病中的作用及机制，为研究和治疗NB提供新的策略和靶点 。