STZ诱导的1型糖尿病小鼠脑动脉平滑肌细胞Ryanodine受体/通道的功能改变及其机制

项目名称： STZ诱导的1型糖尿病小鼠脑动脉平滑肌细胞Ryanodine受体/通道的功能改变及其机制

项目编号： No.30800432

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 董玲

作者单位： 中国人民解放军第四军医大学

项目金额： 20万元

中文摘要： 申请者首次发现糖尿病小鼠脑血管平滑肌细胞上BKCa通道蛋白的表达和功能亚基的异常使得血管的功能改变。本课题试图解答血管平滑肌细胞钙离子相关通道如BKCa、RyR通道在糖尿病状态下的功能改变和可能的生物学效应。因此课题组从糖尿病血管平滑肌细胞上自由基调控BKCa通道的电压依赖性、钙离子依赖性以及下游可能的平滑肌细胞增殖、凋亡机制，结合电生理学、细胞生物学、药理学、检测通道电流、蛋白表达及活性分析、细胞的增殖、凋亡及细胞内自由基水平检测等方法，探讨糖尿病血管平滑肌细胞内钙的改变及调控。研究包括：①#36827;一步探讨自由基对糖尿病血管平滑肌BKCa 通道功能的影响②#30740;究BKCa通道功能的改变除血管收缩舒张功能改变之外对平滑肌细胞凋亡的影响。研究结果部分为我们前期提出血管平滑肌细胞参与糖尿病血管功能及其平滑肌钙调控机制提供理论依据，期望更进一步为临床更有效防治糖尿病血管功能异常提供新资料和实验依据。

中文关键词： 糖尿病；血管平滑肌；钙离子；离子通道

英文摘要： We have previously found that functional and molecular evidence for impairment of calcium-activated potassium channels in type-1 diabetic cerebral artery smooth muscle cells. In the present study, we will focus on further elucidating the calcium related ion channel such as BKCa and RyR channel in diabetic vascular disease and the underlying mechanism using the combination of detecting signaling protein phosphorylation and cell functional studies, which mainly includes:①o tested the hypothesis that reactive oxygen species would regulate the function of BKCa in diabetic cerebral artery smooth muscle cells. The macroscopic BKCa currents decreased in diabetic mice, whereas the currents were partially recovered in the rotenone-treated diabetic mice. ②To investigate the role of BKCa in apoptosis in the diabetic vascular smooth muscle cells. We analyzed the impact of the NO-induced activation of cloned BKCa channels on apoptosis. This study will be directed to clarify the importante effect of calcium related channel in smooth muscle cells and its principal signaling mechanism in diabetic animal model. We expect to provide direct experimental evidence for the treatment of diabetic vascular disease.

英文关键词： diabetic mellitus;vascular smooth muscle cells; calcium; ion channel