基于多组学及CLARITY技术研究胃肠“组织RAS”在厚朴排气合剂调控胃肠动力作用中的分子机制

以动力障碍为特征的胃肠功能障碍性疾病(FGIDs)是一类多发且难治性疾病，我国传统医学对FGIDs具有悠久的诊治历史。厚朴排气合剂作为我国中药保护品种，充分的临床及循证医学证据证明其对FGIDs疗效确切。课题组前期的动物实验及网络药理学研究发现，胃肠“组织肾素-血管紧张素系统”，即“组织RAS(TRAS)”与胃肠动力及FGIDs密切相关，厚朴排气合剂在改善胃肠功能障碍的同时，亦能引起AGTR2等胃肠TRAS成分的变化。结合胃肠TRAS与相关疾病研究的最新进展，课题组提出“厚朴排气合剂通过胃肠TRAS调节胃肠动力”的科学假设。考虑中药制剂作用的多成分、多靶点、多途径及整体性等特点，本课题采用多组学及CLARITY技术与qPCR等传统技术相结合，旨在从基因、蛋白和代谢物等不同层面揭示胃肠TRAS在厚朴排气合剂调控胃肠动力作用中的具体分子机制，为FGIDs的治疗提供充分的理论依据和新的研究思路。

Functional gastrointestinal disorders (FGIDs) are a group of common and refractory diseases, which are characterized by gastrointestinal motility disorder. The traditional Chinese medicine (TCM) has a long history of diagnosis and treatment for FGIDs. Houpu paiqi mixture, as one of protected varieties of TCM, has definite curative effects for FGIDs according to the sufficient clinical and evidence-based evidences. Our previous animal experiments and network pharmacology studies showed that the gastrointestinal“tissue renin-angiotensin system”, or TRAS, was closely related to gastrointestinal motility and FGIDs, and the Houpu paiqi mixture could not only improve gastrointestinal dysfunction, but also cause significant changes in gastrointestinal TRAS such as AGTR2. Combined with the latest research progress of gastrointestinal TRAS and related diseases, we proposed the scientific hypothesis that Houpu paiqi mixture can regulate gastrointestinal motility through the gastrointestinal TRAS. Considering the characteristics of multi-component, multi-target, multi-pathway and integrality for TCM, the proteomics, metabolomics and CLARITY technology will be used combined with other traditional techniques such as the qPCR in this project. We aim to reveal the specific molecular mechanism of gastrointestinal TRAS in the regulation of gastrointestinal motility by Houpu paiqi mixture from different levels of gene, protein and metabolite, so as to provide sufficient theoretical basis and new research ideas for the treatment of FGIDs.