基于代谢组学的PK-PD研究阐释麝香保心丸的体内药效物质及其作用机制

项目名称： 基于代谢组学的PK-PD研究阐释麝香保心丸的体内药效物质及其作用机制

项目编号： No.81473327

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 柳润辉

作者单位： 中国人民解放军第二军医大学

项目金额： 78万元

中文摘要： 麝香保心丸是中国药典收录品种，是临床用于治疗冠心病心绞痛的常用药物之一。前期研究中，本课题组对麝香保心丸的化学物质基础、质量控制标准、药理药效等方面进行了深入研究，研究成果已发表SCI论文10篇，申请专利2项。本项目在前期研究基础上，采用基于代谢组学的PK/PD研究进一步阐释麝香保心丸进入体内的药效物质基础及其协同整合作用机制。根据入血成分在全方、单味药及单组分给药情况下的药代动力学差异，结合血清药化研究结果确定其体内药效物质。以代谢组学研究发现的生物标志物为药效指标进行PK/PD建模，构建药效组分与生物标志物关联网络。将药效组分-生物标志物关联网络映射到疾病生物标志物构建药效物质群-生物标志物网络，用Cytoscape可视化并计算网络拓扑参数并分析全方和单味药药代动力学网络的异同，研究多组分协同的药代动力学网络特征，阐释药物-药物的相互作用关系，解析麝香保心丸多组分协同的整合作用机制。

中文关键词： 中药复方；药效物质基础；作用机制；代谢组学；药代/药效

英文摘要： SShexiang Baoxin pill, the Chinese Pharmacopoeia varieties, is one of the commonly used traditional Chinese medicine formula for the treatment of coronary heart disease. In our previous research, chemical constituents, qulity control, and pharmacological effects had been conducted thoroughly. Therefore, 10 SCI papers have been published, and 2 patents been applied on the results of previous studies.On the basis of previous studies, in vivo pharmacodynamic substance and their meachanism research will be further carried out by PK-PD study based on metabonomics approach. Pharmacokinetic study of the blood components of SBP in the formula, single herb and single component dosing conditions will be carried out by comparing the pharmacokinetic differences.In vivo pharmacodynamic substance will be finally screened according to serum pharmacokinetics and comparing pharmacokinetic studies.In this project, the biomarkers are used as pharmacodynamic index for PK/PD study. According to the blood concentration of active components at different time points and the endogenous biomarker concentration relationship, a PK-PD model will be established, and the pharmacodynamic components and biomarkers association networks will be built as well. Using Cytoscape visualization and network topology parameters calculation, the similarities and differences between the formula and single drug pharmacokinetics network will be analyzed. Furthermore, multicomponent synergy pharmacokinetics network characteristics will be studied, and the interaction relationship between drug-drug, integration multicomponent synergic meachanism of Shexiang Baoxin pill will be then clarified.

英文关键词： Traditional Chinese medcine formula;pharmacodynamic substance;meachanism;metabonomics;PK-PD