从肠道菌群-黏膜免疫探究芍药甘草汤治疗哮喘的作用机制和物质基础

Shaoyao-Gancao Tang (SGT) shows specific therapeutic effects of asthma. However, main active ingredients of SGT are proved to be metabolized by intestinal microbiota and have very low bioavailability. This phenomenon is difficult to explain the efficacy of SGT. Present study including Lancet suggests that the occurrence and development of asthma is closely related to intestinal microbiota and mucosal immunity. Based on the pharmacokinetic characteristics of SGT and previous study, it is speculated that SGT might play an important role in asthma through interaction with intestinal microbiota and modulating the intestinal and lung mucosal immune. To clarify this action, the following research is proceeding. Firstly, the pharmacodynamics study of SGT on model rat is carried out to elucidate the mechanisms of SGT treating asthma. It mainly focus on the regulation of SGT on structures of gut microbiota communities and intestinal and lung mucosal immunity. Secondly, pharmacokinetic study and intestinal metabolic profiles including metabolism of the main components of SGT in intestinal content in vivo and the prototypes of metabolites in incubation of SGT with gut microbiota in vitro will be carried out on asthma and normal model of the rat. To uncover the metabolism, pharmacokinetics and metabolic changes in model rat of SGT. Finally, correlation analyses of above would further be performed to identify those bioactive constituents in SGT to regulate intestinal microbiota and mucosal immune. In the end, the new mechanisms and material basis of SGT treating asthma through interaction with intestinal microbiota and regulation of the intestinal and lung mucosal immune would be illuminated. It would be helpful to offer scientific evidence for precision medication of SGT in the clinic and the selection and development of new SGT formulations. In addition, it would reveal part of the scientific connotation of "the lung and the large intestine are interior-exterior" and provide some experimental evidence to explain this traditional chinese medical theory.

芍药甘草汤（SGT）治疗哮喘，疗效肯定，但其主要成分易被肠道菌群代谢，生物利用度很低，难以从吸收入血解释其药效。目前Lancet等研究发现哮喘发生发展与肠道菌群和黏膜免疫密切相关。基于SGT药动学特点和前期研究基础，提出SGT与肠道菌群相互作用，调节肠肺黏膜免疫治疗哮喘的假说。为此，拟开展以下研究：首先，采用模型大鼠进行SGT治疗哮喘的药效研究，重点观察SGT对肠道菌群结构和肠肺黏膜免疫的调节作用，阐释其作用机制；然后采用正常和哮喘模型大鼠、肠道菌共孵育等体内外方法进行SGT代谢谱研究，阐明其代谢产物、药动学及病理状态代谢谱变化；最后将药效与代谢谱进行相关性分析，辨识SGT调节肠道菌群和黏膜免疫起效的物质。阐明SGT与肠道菌群相互作用，调节肠肺黏膜免疫治疗哮喘的新机制和药效物质，为SGT的临床精准用药和适宜剂型的开发提供科学依据；为中医“肺与大肠相表里”部分科学内涵的诠释提供实验依据。

芍药甘草汤（SGT）治疗哮喘，疗效肯定，但其主要成分易被肠道菌群代谢，生物利用度很低，难以从吸收入血解释其药效。目前Lancet等研究发现哮喘发生发展与肠道菌群和黏膜免疫密切相关。基于SGT药动学特点和前期研究基础，提出SGT与肠道菌群相互作用，调节肠肺黏膜免疫治疗哮喘的假说。为此，开展以下研究：首先，采用模型大鼠进行SGT治疗哮喘的药效研究，重点观察SGT对肠道菌群结构和肠肺黏膜免疫的调节作用，阐释其作用机制；然后采用正常和哮喘模型大鼠、肠道菌共孵育等体内外方法进行SGT代谢谱研究，阐明其代谢产物、药动学及病理状态代谢谱变化；最后将药效与代谢谱进行相关性分析，辨识SGT调节肠道菌群和黏膜免疫起效的物质。结果表明，SGT可以调整哮喘大鼠肠、肺组织中Th1/Th2相关因子及其平衡，调节肠道菌群。SGT主要成分在哮喘和正常大鼠的体内外代谢不同，通过药效和代谢谱进行相关性分析，辨识了其主要有效成分。最终阐明SGT与肠道菌群相互作用，调节肠肺黏膜免疫治疗哮喘的新机制和药效物质，为SGT的临床精准用药和适宜剂型的开发提供科学依据；为中医“肺与大肠相表里”部分科学内涵的诠释提供实验依据。