基于功能代谢组学探讨薏苡附子散治疗类风湿性关节炎和慢性心力衰竭“异病同治”的生物学机制

"Homotherapy for Heteropathy" is one of the characteristics of syndrome differentiation and treatment. Since both of them exhibit cold and wet resistance syndrome to a certain extent, rheumatoid arthritis (RA) and chronic heart failure (CHF) are usually treated with the traditional prescription Yiyi Fuzi Powder. However, there are two key issues to be addressed urgently for the "Homotherapy for Heteropathy" of Yiyi Fuzi Powder: firstly, the material basis of disease is not clear, lacking in elucidation by modern scientific language; secondly, few information was available about the dynamic process of disease outcome and initiation after Chinese medicine intervention. In order to explain the biological mechanism of the "homotherapy for heteropathy" of Yiyi Fuzi Powder, this project intends to study the metabolic biomarkers, and molecular mechanism of "homotherapy for heteropathy" from the point of view of endogenous metabolites regulation. The successful completion of this project not only clarifies the molecular mechanism of the treatment of RA and CHF with Yiyi Fuzi Powder, but provides a new research idea for the scientific interpretation of the thought of TCM syndrome differentiation and administration.

“异病同治”是中医辨证论治的特色之一，类风湿性关节炎（RA）和慢性心衰（CHF）一定程度均表现出寒湿互结，中医常以温阳利水方剂-薏苡附子散进行治疗。然而薏苡附子散“异病同治”存在两个关键问题亟需解决：一是病机物质基础尚不清晰，缺乏现代科学语言进行阐释；二是中药干预后疾病转归及启动的动态过程是怎样的？为了阐释薏苡附子散“异病同治”的生物学机制，根据疾病及转归的脂质代谢特征，本课题拟从内源性代谢物调控角度出发，借助功能代谢组学、DARTS及分子生物学等多种手段，发现“异病同治”病机的代谢生物标志物、疾病转归的启动点（直接靶标）及分子机制。本课题的顺利完成不仅明确薏苡附子散治疗RA和CHF“异病同治”的分子机制，更为科学阐释中医辨证论治思想提供一条新的研究思路。

按照申请书内容，本课题计划取得如下进展：（1）建立了基于代谢组学技术药物研究方法，明确薏苡附子散干预类风湿性关节炎和慢性心力衰竭的治疗作用研究。（2）应用GC-MS技术建立脂肪酸靶向代谢组学，筛选出可能的生物标志物。（3）基于网络药理学和代谢组学整合分析薏苡附子散异病同治RA和CHD的共性机制研究，发现VEGF-cPLA2-AA是YYFZ异病同治的潜在起效机制。（4）经体内、体外实验验证，确证薏苡附子散“异病同治”转归的分子机制。本课题的顺利完成不仅明确薏苡附子散治疗RA和CHF“异病同治”的分子机制，更为科学阐释中医辨证论治思想提供一条新的研究思路。发表SCI论文2篇，中文文章4篇，另有1篇SCI论文在投，1篇中文文章在投。