从ABCA1表达的JAK/STAT3信号通路探讨何首乌蒽醌类成分抗动脉粥样硬化的作用机制

项目名称： 从ABCA1表达的JAK/STAT3信号通路探讨何首乌蒽醌类成分抗动脉粥样硬化的作用机制

项目编号： No.81460670

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王和生

作者单位： 贵州中医药大学

项目金额： 48万元

中文摘要： 本研究以传统补肝肾、益精血的贵州道地药材何首乌中的游离蒽醌为研究对象，以胆固醇代谢和炎症反应相互交汇的动脉粥样硬化(AS)早期事件为切入点，以三磷酸腺苷结合盒转运体A1（ABCA1）为靶点，通过何首乌游离蒽醌有效成分干预ApoE-/-小鼠AS模型及其巨噬细胞泡沫化过程中细胞内胆固醇外流，观察ABCA1、NF-κB、TNF-α、LI-1β、IL-6表达及冠状动脉粥样斑块稳定性和病理学改变。结合细胞培养、分子生物学及蛋白质显微共定位技术，探讨其对ABCA1介导胆固醇外流及激活JAK2/STAT3信号通路的影响，阐明何首乌作为防治AS的的作用机制，为实现地方药物资源的利用及疾病的防治提供新思路和实验依据，具有重要的理论意义和新药开发研究指导价值。

中文关键词： 动脉粥样硬化；信号通路；何首乌；游离蒽醌

英文摘要： In this study, we use the traditional tonifying the liver and kidney, beneficial essencehematic Guizhou authentic ingredients in Radix Polygoni Multiflori free anthraquinone as the research object, the early event Atherosclerosis (AS) cross each other in cholesterol metabolism and inflammation as the breakthrough point, ATP-binding cassette transporter A1(ABCA1) as target, through Polygonum multiflorum free intracellular cholesterol efflux of anthraquinone in effective components of intervention in ApoE-/- mice AS model and foamy macrophages process, to observe the changes of NF- κB、ABCA1、TNF- α、 LI-1 β、IL-6 expression and coronary atherosclerotic plaque stability and patholo Combined with the cell culture, molecular biology and protein micro co localization technology, in-depth study of the mediated effects on cholesterol efflux and the activation of JAK2/STAT3 signaling pathway on ABCA1 dielectric, clarify the Polygonum multiflorum Thunb as the prevention of mechanism of anti AS drug, to provide new ideas and experimental basis for the prevention and treatment of diseases using and local drug resources, has the theory significance and the development of new drugs important guiding value.

英文关键词： antiatherosclerotic;signaling pathway;Polyonum multiforum;anthraquinones