淫羊藿苷预防AD的线粒体途径的作用机制研究

项目名称： 淫羊藿苷预防AD的线粒体途径的作用机制研究

项目编号： No.81202192

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 贺晓丽

作者单位： 中国医学科学院药用植物研究所

项目金额： 23万元

中文摘要： 随着人口的老龄化，我国AD患病率逐年增高，AD中的氧应激损伤、能量代谢缺陷以及钙离子稳态失衡等都与线粒体密不可分，AD 病人线粒体功能异常已经成为研究热点。雌激素具有明确改善学习记忆的作用，最新研究证明线粒体是雌激素作用的主要靶标，雌激素能直接影响线粒体功能，但确切的作用机制目前尚不清楚。本研究拟以SAMP8小鼠为模型，选择已确证具有雌激素样生物活性的淫羊藿苷(ICA)预防给药，以雌激素受体拮抗剂和线粒体抑制剂为工具药，通过整体和细胞两个层面，观察雌激素和线粒体之间的交互作用。通过线粒体多种检测指标研究ICA预防给药对线粒体功能的影响，通过Real-time PCR研究线粒体特异性损伤模型下ICA雌激素样作用的作用靶点，通过线粒体蛋白质组实验研究ICA雌激素样作用的线粒体途径，从而探讨ICA预防AD学习记忆障碍中的线粒体作用机制。为抗AD药物的开发和利用奠定基础。

中文关键词： 阿尔茨海默病；淫羊藿苷；线粒体；雌激素样作用；学习记忆

英文摘要： With the life expectancy of human beings, the prevalence of Alzheimer's disease in Elders in China increased year by year. Neuron viability and defense against neurodegenerative disease can be achieved by targeting mitochondrial function to reduce oxidative stress, or promote energetic metabolism and calcium ion homeostasis. Mitochondrial dysfunction in AD patients has become a hot topic. Estrogen was proved to be beneficial to patients with AD by epidemiological and experimental research, and the latest studies have shown that mitochondria act as therapeutic targets of estrogen action in the central nervous system. Estrogen can directly affect mitochondrial function, but the exact mechanism is not clear. This study used SAMP8 mice as a novel aging model which exhibits many features that are known to occur early in the pathogenesis of AD, preventive administrated of icariin (ICA) which has proved to have estrogen-like biological activity, using the estrogen receptor antagonist and mitochondrial inhibitor drugs, to observe the prevention activities of ICA on the pathogenesis of AD through the mitochondrial pathway. Mitochondrial multiple indexes were used to study the preventive effect of ICA on mitochondrial function, Real-time PCR assays were used to find the specific mitochondrial targets of ICA in mitochondri

英文关键词： Alzheimer’s disease；icariin；mitochondria；estrogen-like effect；learning and memory