基于“脑-肠-菌轴”的枳术丸中用生制白术的炮制机理研究

The study on the processing mechanisms of Chinese medicine in Chinese medicine formula is an important basis to ensure the rational use of Chinese medicine in clinical. Zhizhu pills have been regards as an effected Chinese medicine formula on functional dyspepsia. However, the employment of raw or processed Atractylodis Macrocephalae Rhizoma in Zhizhu pills is quite confused, which largely affects its curative effects in clinic. So, correlation study will be carried out which under the guidance of TCM theory..Firstly, chromatographic technique and multivariate statistical analysis were combined to explore the changes of chemical composition in Zhizhu pills which cause by the processing of Atractylodis Macrocephalae Rhizoma. .Secondly, serum pharmacochemistry and pharmacokinetics were combined to explore the effects of blood transitional components and absorption characteristic about active components in Zhizhu pills which cause by the processing of Atractylodis Macrocephalae Rhizoma. That will explore the processing mechanisms of raw and processed Atractylodis Macrocephalae Rhizoma which should be used in Zhizhu pills from the direction of pharmacodynamic basis..Thirdly, we are based on the "brain - gut - bacteria axis" which was the main pathogenesis of functional gastrointestinal diseases. The differences of model animals in gastrointestinal function will be compared which cause by the processing of Atractylodis Macrocephalae Rhizoma. It will explore the processing mechanisms of raw and processed Atractylodis Macrocephalae Rhizoma which should be used in Zhizhu pills from the direction of pharmacodynamics..Finally, the research of targeted and non-targeted metabolomics, pharmacodynamic basis and pharmacodynamics will combined to allows a comprehensive understanding of the processing mechanism of raw and processed Atractylodis Macrocephalae Rhizoma which should be used in Zhizhu pills.

研究复方中单味药的炮制机理是保证中医临床合理用药的重要基础。枳术丸是中医治疗功能性消化不良（FD）的良方，但方中使用白术生制品的情况极为混乱，严重影响了其临床疗效。鉴此，本项目在中医药理论的指导下，将色谱技术与多元统计分析方法相结合，考察白术炮制对枳术丸中化学成分的影响；将血清药物化学和药代动力学研究相结合，考察白术炮制对枳术丸中化学成分吸收、分布及代谢情况的影响，从体内外物质基础的角度探讨枳术丸中用生制白术的炮制机理。围绕“脑-肠-菌轴”考察白术炮制对枳术丸改善FD模型动物胃肠功能作用的影响，从药效作用的角度解析枳术丸中用生制白术的炮制机理。最后，通过靶向及非靶向代谢组学研究，比较生制白术制枳术丸对FD模型动物内源性代谢物影响的差异，再与体内外物质基础和药效作用的研究相关联，以明确枳术丸中用生白术还是制白术进行组方，并深入解析其中的炮制机理。

目前，复方中单味药的炮制品使用极其混乱，是否使用炮制品主要依靠中医的临床经验，而无科学的理论依据。因此，开展复方中单味药炮制机理的研究对于保证中医临床合理用药以及促进中医药的现代化都具有积极的意义。本项目选取组方精简、疗效显著的枳术丸，以方中应用白术生制品为代表，以功能性消化不良（FD）为病症，按照“炮制-配伍-物质-药效-代谢”的研究模式，将色谱技术与多元统计分析方法相结合，考察白术炮制对枳术丸中化学成分的影响，发现麸炒可以改变白术中挥发性及非挥发性成分的组成及含量，并在与麸炒枳实配伍后影响枳术丸的化学组成及含量；将血清药物化学和药代动力学研究相结合，考察白术炮制对枳术丸中化学成分吸收、分布及代谢情况的影响，发现应用麸炒白术制枳术丸更利于倍半萜及黄酮类成分吸收入血，并从血液分布到组织，还可增加有效成分的原型排泄量，从而减少对肾脏的损伤。围绕“脑-肠-菌轴”探讨枳术丸治疗FD药效作用机制，并考察白术炮制对枳术丸药效作用的影响，发现枳术丸对FD的治疗作用可通过恢复肠粘膜屏障完整性和抑制炎症反应而实现，并且麸白术制枳术丸的作用优于生白术制枳术丸的作用。最后，通过靶向及非靶向代谢组学研究，比较生制白术制枳术丸对FD模型动物内源性代谢物影响的差异，发现麸炒白术及麸白术制枳术丸对FD模型动物体内差异性标志物的回调作用优于生白术制枳术丸。综上，通过本项目的研究，初步明确了枳术丸治疗功能性消化不良应该使用麸炒白术更有效。同时，本项目的研究成果及研究思路也为中药炮制原理以及中药复方现代化的研究和功能性消化不良疾病的防治提供了方法的借鉴和理论的依据。