基于微透析在线分析技术和代谢组学方法的人参远志配伍治疗阿尔茨海默病的药效物质基础和作用机制研究

项目名称： 基于微透析在线分析技术和代谢组学方法的人参远志配伍治疗阿尔茨海默病的药效物质基础和作用机制研究

项目编号： No.21505048

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张艳

作者单位： 吉林化工学院

项目金额： 21万元

中文摘要： 阿尔茨海默病（Alzheimer’s disease，AD）是一种以认知功能减退为主要症状的老年性疾病，中药在治疗AD上历史悠久，然而由于中药成分复杂、作用靶点多样，限制了其在治疗AD中的应用，开发中药治疗AD是当今热点之一。本项目将传统治疗健忘痴呆的中药人参和远志配伍，建立微透析-超高效液相色谱/质谱在线联用分析方法，借助药动学-药效学模型，研究人参远志配伍药对入血、入脑代谢物组在AD大鼠体内的药代动力学规律，旨在解释人参远志配伍治疗AD的药效物质基础；并借助代谢组学研究方法考察相关内源性生物标志物的变化，阐明人参配伍治疗AD的合理比例和整体作用机制。本研究充分发挥微透析技术原位取样、无需样品预处理、动态检测等优点，建立的微透析超高效液相色谱/质谱在线联用分析方法有望对中药治疗AD的研究提供强有力的技术支撑。

中文关键词： 微透析在线分析技术；代谢组学；阿尔茨海默病；药效物质基础；作用机制

英文摘要： Alzheimer’s disease (AD) is an age-related disease characterized in cognitive declining. The traditional Chinese medicine has significant application for treatment of AD. However, it is quite difficult to study their overall mechanism of action because of its complex composition and multi targets. It is a hot spot to develop natural medicine to treat AD. In this study, traditional Chinese medicine Ginseng and Polygala tenuifolia were combined as compatibilities. We employed an online method to combine microdialysis technology and liquid chromatography -mass spectrometry, established a pharmacokinetics-pharmacodynamics model to research pharmacokinetics rules of compatibilities metabolites group in the blood and brain of AD rats, in order to explain the pharmacodynamic material basis of compatibilities for treating AD. We applied a metabolomics method for determining the potential biomarkers to study the overall mechanism of compatibilities for treating AD and the reasonable compatibility proportion. The online combined microdialysis -liquid chromatography -mass spectrometry method with the advantage of samping in situ, monitoring detection and no sampling pretreatment is expected to provide strong technical support for studing the overall mechanism of action for treating AD of the traditional Chinese medicine.

英文关键词： online microdialysis analytical technology;metabonomics;Alzheimer’s disease;pharmacodynamic material basis;mechanism of action