基于代谢组学的人参皂苷治疗阿尔茨海默病的机制研究

项目名称： 基于代谢组学的人参皂苷治疗阿尔茨海默病的机制研究

项目编号： No.81203002

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： 李乃静

作者单位： 中国医科大学

项目金额： 22万元

中文摘要： 阿尔茨海默病（AD）是严重威胁老年人生命的主要疾病之一，人参皂苷Rg1、Rg2、Rb1对AD有良好的治疗作用，但其作用机制尚未完全阐明，尤其是人参皂苷对AD代谢物生物标记物的作用尚未见文献报道。我们的前期研究确定了AD患者血浆中溶血卵磷脂胆碱、鞘胺醇、色氨酸等9个生物标记物。在此基础上，本课题拟以APP/PS1双转基因AD小鼠为研究对象，采用代谢组学的研究方法和手段，通过对AD小鼠及正常对照组小鼠血液、尿液代谢物指纹图谱的分析，确定AD小鼠血液、尿液代谢物的生物标记物。进一步研究人参皂苷Rg1、Rg2、Rb1对AD小鼠体内生物标记物的调控作用，阐释人参皂苷Rg1、Rg2、Rb1治疗AD的作用机理。并采用相关分析等数学统计学方法，建立AD-代谢物-人参皂苷Rg1、Rg2、Rb1疗效相关性评价方法。本课题是从新的视角阐释人参皂苷对AD的作用机制，为早期诊断和中药治疗AD提供理论和实践依据。

中文关键词： 阿尔茨海默病；代谢组学；生物标记物；超高效液相液质联用；

英文摘要： Alzheimer's disease (AD) is one of the leading cause of morbidity in the elderly. Ginsenosides have good effects on AD, but the mechanism has not been fully understood, and the effects of ginsenoside on biomarkers of AD have not been reported. In our prophase research, we have found nine potential biomarkers such as LPCs,sphingosine and tryptophan,etc, all of them could be in correlation with the extent of AD patients. This study taking APP/PS1 transgenic mouse as the research object, attempts to determinate the high sensitive and high specific biomarkers for AD by analyzing metabolic fingerprint of the plasma and urine samples from AD mouse and control mouse based on metabolomics. Furthermore illustrate the mechanism of ginsenosides Rg1、Rg2、Rb1 treatment in Alzheimer's disease based on metabolomics. In addition, establish the evaluating methods for the relativity to explore the relationship between AD and metabolites and ginsenosides Rg1、Rg2、Rb1.Our study attempts to investigate the mechanism of ginsenoside treatment in Alzheimer's disease from a new perspective.The results will be used to assist physicians in fast diagnosis and early treatment of AD, and to provide theoretical basis for researching on the mechanisms of new drugs.

英文关键词： Alzheimer's disease；metabolomics；biomarkers；UPLC-MS/MS；