基于生物药剂学无标度复杂网络模式的中药复方(血脂宁)配伍的分子作用机制研究

After syndrome differentiation, TCM select the appropriate medication to conduct compatibility in accordance with the principle of "monarch, minister, assistant and guide", in order to increase efficacy and reduce toxicity of the traditional Chinese medicine, which is called Chinese herbal compound. Therefore, it is an key issue of the research about the traditional Chinese medicine to clarify the mechanism of Chinese herbal compound compatibility in scientific words. This project intends to use the Chinese herbal compound Xue-Zhi-Ning as a model drug. Firstly, we screen the active chemical components contained in Xue Zhi Ning in high speed based on the clinical efficacy; and then carry out the systematic studys about the influences of the active ingredient biopharmaceutics properties by adding medicine analysis, which is coursed by compatibility; subsequently, it is time to conduct comprehensive evaluation about the trend of compatibility by using a novel method combined with multivariate mathematical statistical model and Quadrant analysis; Finally, the model of scale-free community structure of complex networks will be applied to the study of factorial analysis on compatibility mechanism. In the way of mathematics, standardization and modeling to describe the relation of "point" ( active ingredient ) , "surface" (characteristics of pharmacy ) , " network" ( interaction ) in the process of Chinese herbal compound compatibility. Expected to establish a research method based on the complex network of biopharmaceutics properties, which could be used in the study for traditional Chinese medicine compatibility. It is our expectation that with the help of mathematical "scientific language ", riching scientific connotation of Chinese herbal compound compatibility process, and providing new ideas and methods for the study of the basic theory of traditional Chinese medicine .

中药复方是在中医辨证审因决定治法以后，选择合适的药物按照"君臣佐使"的原则配伍而成的一组药物，以达到增效减毒的目的。因此，科学阐述中药复方配伍规律是中医药研究关键问题之一。本项目拟以中药复方血脂宁为模型药物，首先基于临床疗效对其中成分进行体外活性快速筛选；进而采用加药分析法系统研究配伍过程对活性成分生物药剂学属性的影响，利用多元数理统计模型结合象限分析进行配伍作用趋势评价；最后采用无标度的社团结构复杂网络模式对配伍机制进行析因分析。以数学化、标准化、模型化的方法描述中药复方配伍过程的"点"(活性成分)、"面"(药剂学特征)、"网"(相互作用)的作用关系。预期建立一种基于生物药剂学特征复杂网络模式的中药复方配伍机制研究方法，借助数学的"科学语言"丰富中药复方配伍的科学内涵，为中医药基本理论研究提供新的研究思路。

本课题立足于现代中药核心问题——中药复方配伍规律的科学阐释，提出了一种基于生物药剂学特征复杂网络模式的中药复方配伍机制研究方法。以中药复方血脂宁为模型药物，首先基于临床疗效对复方中成分进行了体外活性筛选，建立了基于多种体外抗氧化活性测定的降脂保肝活性成分快速筛选方法；将化学计量学与超高效液相指纹图谱、超高效液相色谱-高分辨飞行时间质谱(UPLC-Q-TOF/MS)相结合，可实现对复方血脂宁、何首乌、决明子、山楂、荷叶中多成分的定性分析与定量分析；采用加药分析法系统研究了配伍过程对活性成分生物药剂学属性的影响，从分子作用层次研究了配伍对活性成分生物药剂学特征的影响；利用多元数理统计模型结合象限分析对配伍作用进行了评价，并建立了基于生物药剂学特征复杂网络模式的复方血脂宁配伍机制研究方法。为中药复方的配伍理论研究提供了新的思路和实验范例。