基于NMR代谢组学对肝豆灵排铜作用机制的研究

项目名称： 基于NMR代谢组学对肝豆灵排铜作用机制的研究

项目编号： No.81202691

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： 蒋怀周

作者单位： 安徽中医药大学

项目金额： 23万元

中文摘要： Wilson病（WD）是一种与铜代谢障碍有关的神经系统疾病，肝豆灵片是中医药治疗WD的有效制剂，但对该复方排铜作用机制的研究仍处于探索阶段。代谢组学技术是系统生物学的研究方法之一，它可以从整体的、动态的角度来研究药物对生物体的作用机制,这一特点非常符合中医治疗疾病的整体观念。前期研究证明，基于核磁共振的代谢组学研究方法可分析出中医复方在生物体内的代谢产物，通过对这些代谢产物的分析，可逆向推测出复方在生物体内的干预网络，进而分析其作用机制。本研究将运用此技术进行以下研究：建立肝豆灵干预铜负荷大鼠的核磁共振谱；对肝豆灵的生物代谢产物进行定性定量分析,筛模型大鼠血清、尿液中能够反应其排铜效果的特征代谢物，并分析肝豆灵对这些特征代谢物的影响；探讨肝豆灵对铜负荷大鼠代谢网络的修复途径；最终，利用代谢组学的理论、参照文献探讨肝豆灵的排铜作用机理，为中医药治疗WD的排铜机制研究提供新的思路和参考。

中文关键词： 代谢组学；代谢物；肝豆灵；排铜机制；肝豆状核变性

英文摘要： Wilson's disease is a neurological disease caused by copper dismetabolism. Gandouling tabelet is an effective traditional Chinese preparation in treating Wilson's disease. However, its mechanism of action is still on the exploratory stage. As a systematic biology research method, metabonomics studies the mechanism of drugs on organisms from a holistic, dynamic point of view, which accords with the overall concept of Chinese medicine treatment of diseases. Preliminary studies have shown that metabolites of Chinese preparation can be detected and analyzed through NMR-based metabonomics, analysis of these metabolites can reversely speculate the intervention network of Chinese preparation in vivo, and thus the mechanism of drugs can be analyzed. This study will use NMR-based metabonomics to conduct the following studies: to establish NMR spectroscopy of the treatment mechanism of Gandouling on copper-loaded rat, to conduct qualitative and quantitative analysis on biological metabolites of Gandouling, to screen the characteristic metabolites in model rats' urine and blood that can reflect the curative effect, and analyze the effect of Gandouling on these characteristic metabolites, to explore the metabonomic restoration approach of Gandouling on the model rats, to explore the treatment mechanism of Gandouling on the

英文关键词： metabonomics；metabolite；Gandouling；copper elimination mechanism；Wilson disease