从内质网应激探讨虎杖苷、山楂总黄酮配伍抗动脉粥样硬化机制

项目名称： 从内质网应激探讨虎杖苷、山楂总黄酮配伍抗动脉粥样硬化机制

项目编号： No.81202805

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： 吴敏

作者单位： 中国中医科学院广安门医院

项目金额： 23万元

中文摘要： 课题组前期研究发现基于"瘀毒"病机的解毒活血中药组分配伍（虎杖苷配伍山楂总黄酮）治疗AS疗效明确，我们推测其可能机制是：通过调控内质网稳态， 细胞凋亡、炎症因子表达、血脂代谢及内皮功能，从而发挥抗AS作用- - -本课题以载脂蛋白E基因敲除小鼠为AS模型，体内与体外试验相结合，应用现代生物信息学和生物学前沿技术，从内质网激活标记蛋白GRP78、GRP94表达、细胞凋亡、炎性因子活性与表达、脂代谢变化以及AS斑块形态学改变，从结构与功能角度探讨虎杖苷、山楂总黄酮及其配伍对AS斑块形成及内质网激活状态的影响，探讨该活性组分配伍抗AS的分子机制，验证假说的客观性，研究结果为从一个侧面阐释解毒活血治疗AS的理论内涵，提供了原创性实验依据，在中医药AS的防治研究中未见同类报道。

中文关键词： 内质网应激；解毒活血；动脉粥样硬化；虎杖苷；山楂总黄酮

英文摘要： We found that the toxin-resolving prescription（Polydatin and extraction of Hawthorn）based on"stasis-toxin" pathogenisis had good clinical effect and safety in treating atherosclerosis, and its anti-atherosclerosis mechanism might be related to the regulation of endoplasmic reticulum stress pathway, apoptosis, expression of inflammatory factors, lipid metabolism, endothelium function. This study will choose APOE gene knockout mice as the model of atherosclerosis. It includes two parts, vivo and vitro studys. The protein of epression of GRP78,GRP94, apoptosis, the expression of inflammatory factor, lipid metabolism and the morphology changes of plaque will be detected. The mechanism of anti-atherosclerosis with Polydatin and extraction of Hawthorn will be found through endoplasmic reticulum stress pathway. The finding will explain the connotation of blood-activating and toxin-resolving prescription based on"stasis-toxin" pathogenisis. And we have not found the same report in the prevention and cure of atheroscelrosis in TCM.

英文关键词： endoplasmic reticulum stress；blood-activating and toxin-resloving prescription；atherosclerosis；polydatin；extraction of Hawthorn