一种新的平滑肌收缩机制研究

项目名称： 一种新的平滑肌收缩机制研究

项目编号： No.31501864

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 乔艳宁

作者单位： 陕西师范大学

项目金额： 22万元

中文摘要： 平滑肌广泛分布于动物的空腔脏器（如：胃肠、血管、呼吸道等），收缩是其基本功能，研究平滑肌的收缩机制，对平滑肌相关疾病的发病机制研究、防治具有重要意义。业已证实，肌球蛋白轻链（RLC）磷酸化是各种平滑肌收缩的必须事件。在前期研究中我们意外地发现，当RLC敲除后，平滑肌仍保持对刺激的收缩应答，并且表现出独特的收缩特征。由此，我们推测：平滑肌还存在有RLC非依赖性收缩，这种新的收缩机制可能在生理、病理过程中仍发挥着某种功能。本申请项目提出假说：平滑肌中存在RLC非依赖性收缩机制，该收缩机制有可能与细丝调节信号通路有关。为此，本课题拟通过小鼠模型，分别从遗传学、生理学、细胞生物学等角度，系统阐明该收缩行为的形成机制以及与疾病的关系。本项目预期结果，将发现一个新的平滑肌收缩模式，同时也为平滑肌性疾病的发病机制及干预方法研究提供新的思路。

中文关键词： 平滑肌；收缩；肌球蛋白调节轻链；基因敲除小鼠模型；胃肠动力学障碍

英文摘要： Smooth muscle is widely distributed in the body and its contractility serves the base of physiological function of gastrointestinal, vascular and respiratory systems. Elucidation for contractile properties and their regulatory mechanism are essential for understanding pathogenesis as well as developing therapeutic strategies. Our previous reports with MLCK knockout mice show that myosin light chain phosphorylation is the central for regulation of smooth muscle contraction. However, when we deleted RLC specifically in smooth muscle, smooth muscle still showed featured contractility after stimulation. We thus speculate that smooth muscle might also able to contract with a mechanism independent of myosin light chain phosphorylation. In this study, we will investigate the mechanistic regulation of such a contraction through a series of knockout mice as well as analysis of physiology, genetic, cell biology. Our expected results will shed insight into a novel mechanism for smooth muscle contraction thereby providing new therapeutic strategy and pathogenesis for smooth muscle diseases.

英文关键词： Smooth muscle;Contraction;Myosin regulatory light chain;Gene Knockout mouse model;Gastrointestinal disorder