基于线粒体蛋白质组学的针刺治疗阿尔茨海默病的分子机制研究

项目名称： 基于线粒体蛋白质组学的针刺治疗阿尔茨海默病的分子机制研究

项目编号： No.81202730

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： 朱宏

作者单位： 中南大学

项目金额： 23万元

中文摘要： 研究表明氧化应激是AD患者脑内最早发生的病理事件，线粒体是细胞内氧自由基的主要来源，在AD患者脑内氧化应激反应中占据中心地位，有学者据此提出了AD发病机制的"线粒体级联假说"，成为了近些年AD研究的热点。补肾活血针刺法取肾俞、百会、血海、膈俞为基本穴位，前期研究表明它能够改善AD患者以及AD模型小鼠的认知功能，采用比较蛋白质组学研究了它对SAMP8小鼠海马蛋白质表达的影响，鉴定出多种与氧化应激相关的差异表达蛋白，如线粒体乌头酸水合酶、细胞色素C氧化酶以及脑红蛋白，说明线粒体可能是补肾活血针刺法发挥治疗作用的主要"亚细胞器靶点"。本项目拟采用亚细胞蛋白质组学、Western Blot、PCR、免疫组化方法比较、鉴定并验证针刺干预后SAMP8小鼠海马线粒体差异蛋白的表达，基于生物信息学方法构建补肾活血针刺法治疗作用的分子信号网络，从亚细胞蛋白研究的角度阐释补肾活血针刺法防治AD的分子生物学机制

中文关键词： 针刺；阿尔茨海默病；快速老化小鼠；线粒体；蛋白质组学

英文摘要： Reaserch shows that oxidative damage is the earliest event in Alzheimer disease.Mitochondria is the main source of free oxygen radicals in cells, occupying a central position in the oxidative stress response in the brain of AD patients. Some scholars thus have proposed the "mitochondrial cascade hypothesis" of AD pathogenesis, a research focus of AD in recent years. Shenshu(BL23), Baihui(GV20), Xuehai(SP10),Geshu(BL17) were selected as the basic acupoints for acupuncture of reinforcing kidney and activating blood. Preliminary studies have shown that it could improve the cognitive function of patients with AD and AD model mice.Comparative proteomics study found that acupuncture intervention affects the protein expression in hippocampus of SAMP8 mice. A variety of differentially expressed proteins related with oxidative stress were identified,such as aconitase, cytochrome C oxidase, and neuroglobin,so mitochondria may be the main subcellular therapeutic target of acupuncture. The present study intends to use subcellular proteomics,western blot, PCR, immunohistochemical methods to identify and verify differences in protein expression of hippocampal mitochondria after acupuncture intervention. Based on bioinformatics methods,we try to build molecular signaling networks of therapeutic targets of acupuncture with no

英文关键词： Acupuncture；Alzheimer’s disease；Senescence accelerated mice；Mitochondria；Proteomics