调肝导浊方调控内皮细胞AMPK通路防治动脉硬化的机制

项目名称： 调肝导浊方调控内皮细胞AMPK通路防治动脉硬化的机制

项目编号： No.81202797

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 郭茂娟

作者单位： 天津中医药大学

项目金额： 23万元

中文摘要： 内皮细胞功能受AMPK通路调节，在氧化性修饰脂蛋白（OX-DL）作用下，抑制AMPK通路，导致内皮细胞功能失调，启动动脉粥样硬化（AS）及心脑血管事件发生。前期研究和临床资料显示"调肝导浊方"具有保护内皮细胞功能、防治AS发生，但机制尚未阐明。提出"调肝导浊方"基于AMPK通路，调节 "内皮功能失调"，防治AS的假说。在体和离体实验相结合，建立ApoE4基因敲除小鼠AS模型和OX-DL致内皮细胞损伤模型，研究"调肝导浊方"是否通过激活AMPK通路上游物质苏氨酸激酶（LKBl），增加内皮细胞AMP/ATP比值从而调节该通路、改善内皮细胞功能；并运用AMPK通路抑制剂Compound C和激动剂AICAR进一步作用于该通路，从正反两个方面验证"调肝导浊方"是否通过调节AMPK通路，改善内皮细胞功能。课题对于阐明调肝导浊中药防治AS的作用机制，为其预防心脑血管事件发生提供证据，具有重要价值。

中文关键词： 调肝导浊方；动脉粥样硬化；内皮功能；AMPK；

英文摘要： Endothelial cell function is regulated by AMPK pathway，under the action of the oxidative modification of lipoprotein ( OX-DL )，Inhibition of the AMPK pathway, leading to endothelial dysfunction, then initiating of atherosclerosis ( AS ) and cardiovascular events. Preliminary studies and clinical data showed" Tiaogandaozhuo Decoction" with the protection of endothelial cell function, preventing and treating of AS, but the mechanism has not been elucidated. So putting forward a hypothesis that preventing the happening of AS. "Tiaogandaozhuo Decoction" regulating of" endothelial dysfunction" on the AMPK pathway.In vivo and in vitro experiments, establishment of ApoE4 AS knockout mouse model and OX-DL induced endothelial cell injury model. Study of" Tiaogandaozhuo Decoction" is through activation of the AMPK pathway upstream material threonine kinase ( LKBl ), increased endothelial AMP / ATP ratio, so as to adjust the channel, improving endothelial cell function. Application of AMPK pathway inhibitor Compound C and agonist AICAR further role in the pathway, from positive and negative two respects verified" Tiaogandaozhuo Decoction" is by adjusting the AMPK pathway, improving endothelial cell function. The subject's aim is to elucidate Tiaogandaozhuo Decoction prevention and treatment of AS's the mechanism, has the i

英文关键词： Tiaogan Daozhuo Decoction；Atherosclerosis；Endothelial function；AMPK；