刘雪婷;陈文佳;刘维;李培豪;胡永昊;林娜;张彦琼;
LIU Xue-ting;CHEN Wen-jia;LIU Wei;LI Pei-hao;HU Yong-hao;LIN Na;ZHANG Yan-qiong;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine;China Resources Sanjiu Medical & Pharmaceutical Co.,Ltd.;

• 1:中国中医科学院中药研究所
• 2:天津中医药大学第一附属医院
• 3:华润三九医药股份有限公司

摘要(Abstract)：

从“病-证-方”关联角度，探索天和追风膏治疗类风湿关节炎(rheumatoid arthritis, RA)寒湿痹阻证的作用机制，并分析膏方中各功效组的配伍特点。首先利用中医药整合药理学研究平台(TCMIP v2.0)获得RA临床症状表型的相关基因集，再通过临床寒湿痹阻证RA患者和健康志愿者对照的转录组表达谱检测及生物信息挖掘，筛选获得RA寒湿痹阻证的差异表达基因集。同时，从TCMIP v2.0和中医药数据库(TCMBank)中，收集天和追风膏所含35味中药材的化学成分信息，并依据化合物结构相似性原理，预测其候选靶标谱。进一步，利用上述病证基因和药物候选靶标的相互作用信息，构建“RA寒湿痹阻证相关基因-天和追风膏候选靶标”互作网络，通过计算网络拓扑特征值，筛选其核心网络靶标，并基于Kyoto Encyclopedia of Genes and Genomes(KEGG)和Reactome Pathway Database(Reactome)通路数据库开展功能挖掘，进一步探索天和追风膏组方中各功效组的配伍机制。研究结果显示，天和追风膏候选靶标所参与的通路主要分布于“免疫-炎症”调节、神经系统功能、细胞功能、物质和能量代谢等模块，且膏方中不同功效组的作用特点各有侧重：祛风除湿-通经活络组、息风止痉组和辛辣止痛组通过散寒邪和温经脉，活血化瘀组和强筋健骨组通过畅血气和通经络，调节“免疫-炎症”系统；祛风除湿-通经活络组、活血化瘀组、强筋健骨组、息风止痉组和清热泻水组通过补气血和益神明影响神经系统；祛风除湿-通经活络组和息风止痉组通过祛风邪和除寒湿、活血化瘀组和强筋健骨组通过通血脉和强筋骨，调节细胞功能、物质和能量代谢。综上，天和追风膏可能通过矫正“免疫-炎症”失衡、调节神经系统和细胞功能，以及干预物质和能量代谢以发挥祛风除湿、活血化瘀、温经通络、强筋健骨的综合功效，并改善RA寒湿痹阻证症状。相关研究结果为明确天和追风膏的疗效特点和临床定位奠定基础。
This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on the "disease-syndrome-formula" association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network of "related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointment" was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules of "immune-inflammation" regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulated "immune-inflammation" system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated "immune-inflammation" system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance of "immune-inflammation", regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

关键词(KeyWords)： 网络药理学;天和追风膏;类风湿关节炎;寒湿痹阻证
network pharmacology;Tianhe Zhuifeng Ointment;rheumatoid arthritis;syndrome of internal obstruction and cold-dampness

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划项目(2018YFC1705201);; 中国中医科学院科技创新工程项目(C12021A03808);中国中医科学院中药研究所技术研发项目(20211008)

作者(Authors): 刘雪婷;陈文佳;刘维;李培豪;胡永昊;林娜;张彦琼;
LIU Xue-ting;CHEN Wen-jia;LIU Wei;LI Pei-hao;HU Yong-hao;LIN Na;ZHANG Yan-qiong;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine;China Resources Sanjiu Medical & Pharmaceutical Co.,Ltd.;

DOI: 10.19540/j.cnki.cjcmm.20220421.402

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