"茯苓-桂枝"药对改善心肌缺血的配伍机制研究

Herb couple is the bridge between simple prescription and compound prescription. To study the mechanism of herb couple can reveal the connotation of compound prescription briefly. The metabolomics reflecting the thought of systemic biology is hoped to provide the effective solving approach to the general evaluation of the herb couple efficacy. This subject will study on the intervention of Fulin-Guizhi activating yang by diuresis function on metabolic net of the chronic myocardial ischemia rats through gas chromatography-mass spectrometry (GC-MS/MS), nuclear magnetic resonance(NMR) technology and orthogonality partial least squares- discriminant analysis(OPLS-DA), applying multiple pattern recognition treated metabonomics method based on Statistical Total Correlation Spectroscopy(STOCSY). We hope to find the biological markers group characterized efficacy and its dynamic change law from the way of energy metabolism, mass transfer and information conduction. It is also hoped to reveal integraly the biological connotation of the mechanism that how the herb couple activate yang by diuresis function analyzing the pharmacological gold indexes at the same time, and furthermore to provide scientific evidence of Chinese traditional medicine preventing and treating coronary heart disease(CHD) which seriously damages human being health and life.

药对是单方和复方之间的桥梁，研究药对的作用机制能驭繁就简地揭示复方配伍内涵；而体现系统生物学思想的代谢组学有望为中药药对的药效整体评价研究提供有效解决途径。因此，本项目拟选择"茯苓-桂枝"这一以苓桂术甘汤为代表的苓桂剂核心药对为研究对象，采用核磁共振技术以及正交偏最小二乘法判别分析(OPLS-DA)等多变量模式识别代谢组学方法， 开展干预大鼠心肌缺血（心阳虚胸痹）模型代谢网络的研究。从能量代谢途径、物质传递途径及信息传导途径确认表征药效的生物标志物群及其动态变化规律，结合药理金指标从整体上分析阐释该药对配伍产生利水通阳作用的药效物质基础与作用机理的生物学内涵进而为中医药防治严重危害人类健康与生命的心血管疾病提供科学依据。

本项目选择“茯苓-桂枝”这一以苓桂术甘汤为代表的苓桂剂核心药对为研究对象，采用核磁共振技术以及正交偏最小二乘法判别分析(OPLS-DA)的多变量模式识别代谢组学方法，开展干预大鼠心肌缺血（心阳虚胸痹）模型代谢网络的研究，寻找到表征茯苓配伍桂枝对改善慢性心肌缺血的药效生物标志物20余种；通过茯苓桂枝配伍引起的生物标志物的差异比较，及与常规药效指标整合分析，明确了茯苓配伍桂枝改善慢性心肌缺血大鼠的整体药效作用；根据茯苓桂枝配伍对代谢途径影响的比较分析，初步阐释茯苓配伍桂枝药效作用机制可能为调节能量代谢及氨基酸代谢异常、保护脂质过氧化损伤等。