组胺H3受体对尿道横纹肌控尿功能的作用与机制

项目名称： 组胺H3受体对尿道横纹肌控尿功能的作用与机制

项目编号： No.81500588

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈燕

作者单位： 郑州大学

项目金额： 18万元

中文摘要： 压力性尿失禁（SUI）是女性的常见病、多发病，目前的治疗方法尚不能彻底解决该病。尿道横纹肌是治疗SUI的关键部位。近年发现组胺H3受体存在并参与平滑肌和心肌的收缩功能。对此，我们前期研究发现在成人尿道横纹肌中存在H3受体；小鼠肌源干细胞C2C12成横纹肌分化过程，H3受体表达呈倍增加；在分化后的细胞中激动该受体可以降低胞浆中钙离子浓度。由此推测，H3受体可能通过调节胞浆钙离子浓度影响横纹肌细胞功能，进而通过尿道横纹肌影响控尿功能。本研究拟从H3受体新视点，通过建立SUI小鼠模型来测量H3受体在SUI和正常小鼠尿道横纹肌的表达差异及病毒载体调控H3受体基因表达验证其对小鼠尿道控尿功能的作用；同时通过C2C12细胞阐明H3受体对胞膜和内质网上钙通道的影响及其在细胞中发挥功能的信号通路。从而在宏观动物和微观细胞分子层面揭示H3受体在横纹肌中的角色，为今后临床诊断治疗SUI等尿道疾病提供新思路。

中文关键词： 压力性尿失禁；尿道横纹肌；H3受体；钙离子通道；信号通路

英文摘要： Stress urinary incontinence (SUI) is a common disease, frequently occurring in women. The current treatment methods cannot completely solve this disease. The urethral striated muscle is the key position to treat SUI. The recent studies found histamine H3 receptor was involved in the smooth muscles and myocardium. Meanwhile, our previous study found the presence of H3 receptor in the adult urethral striated muscle and the folds’ increase expression of H3 receptor in the striated myogenesis of mouse muscle derived stem cells C2C12; additionally, activation of H3 receptor can reduce cytoplasmic calcium ion concentration in differentiated C2C12 cells under contraction evoked by electrical stimulation. Therefore, it is supposed that H3 receptor may influence the function of striated muscle cell by regulating cytoplasmic calcium ion concentration, thereby, to play a role in continence function through the urethral striated muscle. The present study would like to do the research from the new viewpoint of H3 receptor that it would set up the SUI mouse model to compare the expression of H3 receptor in the urethral striated muscle between normal and SUI mice, and to verify if the viral vector modulators of H3 receptor gene in the urethral striated muscle could improve urethral continence function on SUI mice ; additionally, we would verify how H3 receptor affects calcium channels on cell membrane and endoplasmic reticulum, and its functional signal pathway in the cells through differentiated C2C12 cells. Thus, these would help to uncover the role of H3 receptor in the striated muscle from animal’s and cellular molecular levels, which would provide new ideas for the clinical diagnosis and treatment of urethral diseases like SUI in the future.

英文关键词： Stress urinary incontinence;urethral striated muscle;H3 receptor;Calcium channel;signal pathway