IKKα#946;调控高糖诱导血管内皮胰岛素抵抗及功能失常的NF-κ#38750;依赖途径

项目名称： IKKα#946;调控高糖诱导血管内皮胰岛素抵抗及功能失常的NF-κ#38750;依赖途径

项目编号： No.30860111

项目类型： 地区科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 黄起壬

作者单位： 南昌大学

项目金额： 23万元

中文摘要： 血管内皮胰岛素抵抗及功能失常是心脑血管事件共同的病理生理基础，但高糖引起血管内皮胰岛素抵抗及功能失常的机制尚未完全阐明。IKKα#946;是NF-κ#20449;号通路中上游激酶，它参与了炎症、细胞增殖、分化和凋亡等调节。研究认为IKKα#946;以NF-κ#20381;赖途径参与了高糖诱导血管内皮胰岛素抵抗及功能失常的调节，但是否存在NF-κ#38750;依赖机制，目前还未见报道。本研究拟在整体、离体和细胞水平上确认高糖应激是否影响IKKα#946;的表达及活性改变，并观察内皮细胞损伤，血管舒张功能和内分泌功能的变化及与IKKα#946;的关系；并从IRS-1/PI3K/Akt/NO和Raf-1/MAPK/ET-1通路探讨IKKα#946;介导高糖引起血管内皮胰岛素抵抗/功能失常的NF-κ#38750;依赖机制。最后运用基因沉默策略进一步进行确证。旨在进一步探讨糖尿病血管病变的分子机制，为寻找糖尿病血管病变的防治的新分子靶点和治疗策略拓展新的思路。

中文关键词： IKK；NF-κ#65307;内皮细胞；胰岛素抵抗；Raf-1

英文摘要： Insulin resistance and dysfunction in vascular endothelia are a physiological fundamental of cardiovascular and cerebrovascular events.Mechanism underlying insulin resistance and dysfunction induced by hyperglycemia,however, is unclear.IKKa/b,a kinase of NF-KB pathway, is a modulator in inflamation, cell proliferation,differentiation and apoptosis.There is large evidence that IKKa/b is involved in the regulation of endothelial insulin resistance and dysfunction in a manner of NF-KB dependence, but that of NF-KB independence is not reported up to date.This study is first to confirm whether hyperglycemia/high glucose results in changes of IKKa/b expression level and activity, and to observe relation between endothelial dysfunction/injury and IKKa/b in vivo and in vitro.In the end, the mechanism underlying insulin resistance and dysfunction induced by hyperglycemia is studied by use of gene silence though IRS-1/PI3K/Akt/NO and Raf-1/MAPK /ET-1 pathway.The purpose of this study is to further exploit the molecular mechanisms of angiopathy in diabetes mellitus and to provide a new strategy to treat angiopathy of diabetese mellitus.

英文关键词： Inhibitory kB kinase;NF-kB;Endothelial cell; Insulin resistance;Raf-1.