四逆汤药味配伍“毒减而效不减”的机制研究

Sini Decoction is made up of Gancao, Ganjiang and Fuzi, which reflects some basic traditional theories about "mutual-restraint or mutual-assistance" of detoxification and compatibility theories. However, in the majority present researches, some scholars only focus on "reduce poisonous by sweet nature" , "restrict migratory nature by defense" of reduce poisonous effect theory, or only focus on a basic theory of Fuzi can't show good efficiency without Ganjiang. These research metheds can't reflect the macroscopic compatibility theory about "reduce poisonous and keep drug action". In preliminary work, our research group found that there is a close contact between Fuzi-Gancao pair and Fuzi-Ganjiang pair in reduce poisonous and keep drug action aspect, which is associated the forms of active substance and toxic substances in vitro and vivo. Therefore, we put forward point that the three Chinese medicines depend on each other and contain each other so as to reduce poisonous and increase efficiency. This project propose to study the changes of Ganjiang pair Gancao before or not in chemical composition as well as focus on the kinetics of intestinal absorption characters and the components of metabolic behavior. According to the overall concept, macro analyzing the differences of Ganjiang pair Gancao before or not in overall metabolism of heart failure animal model group and heart tissue protein expression. According to the Game theory, build a "Chemical composition - in vivo absorption- component metabolic - omics expression" overall linkage new research pattern in Sini Decoction compatibility theories so as to clarify the macro mechanism of action about drug using.

四逆汤由附子、干姜、甘草组成，既体现了"相畏/相杀"的"减毒"配伍思想，又涵括了"相须/相使"的"增效"配伍规律。目前大多独立研究该方"以甘缓毒""以守约行"减毒作用，或"附子无姜不热"增效作用，未能体现方中"毒减而效存"的宏观配伍理念。课题组前期工作发现：附子-甘草和附子-干姜的减毒和增效作用相依存而非独立，并与其毒效物质基础在体内外存在形式相关联。故提出观点：四逆汤中三味药相互依存而又相互牵制，其减毒而增效作用是综合博弈的结果，体现中医遣方用药之精妙。 采用化学指纹技术研究四逆汤"附子-干姜-甘草"配伍前后化学成分变化，并从体内角度揭示其肠吸收动力学特征、毒效表达与代谢行为；根据中医整体观，对比分析配伍前后对心衰模型动物的代谢组和蛋白组的表达差异；基于"博弈理论"，构建"化学成分-体内吸收-毒效表达-组分代谢-组学表达"整体联动的四逆汤配伍理论研究新模式，以阐释其遣方用药之作用机制。

四逆汤由附子、干姜、甘草组成，既体现了“相畏/相杀”的“减毒”配伍思想，又涵括了“相须/相使”的“增效”配伍规律。目前大多单独研究该方“以甘缓毒”“以守约行”减毒作用，或“附子无姜不热”增效作用，未能体现方中“毒减而效存”的宏观配伍理念。本项目采用化学指纹技术研究四逆汤“附子-干姜-甘草”配伍前后化学成分变化，并从体内角度揭示其肠吸收动力学特征、毒效表达与代谢行为，对比分析配伍前后对心衰模型动物的代谢组和蛋白组的表达差异，从而构建“化学成分-体内吸收-毒效表达-组分代谢-组学表达”整体联动的四逆汤配伍理论研究一种新模式。该研究揭示了四逆汤中三味药相互依存而又相互牵制，其减毒而增效作用是综合博弈的结果，系统诠释了四逆汤遣方用药“毒减而效不减”科学内涵的创新思路，体现中医遣方用药之精妙。迄今为止，本项目在国内外核心期刊共发表研究论文12篇；培养博士研究生1人，硕士研究生3人；参加国际和国内学术会议10人次。