目的 采用网络药理学方法，对芍药甘草汤治疗类风湿关节炎的作用机制进行研究。方法 通过中药系统药理学数据库和分析平台（TCMSP）对芍药甘草汤进行活性成分的收集和筛选，在Swiss Target Prediction和TCMSP数据库中查找活性成分对应的人类靶蛋白；在Drugbank和Therapeutic Target Database数据库中获取类风湿关节炎的疾病靶点；构建韦恩图，得到芍药甘草汤治疗类风湿关节炎的关键靶点，依据STRING数据库得到关键蛋白的蛋白互作网络；采用DAVID数据库对关键靶点进行基因本体论（GO）和通路富集分析，使用Image GP平台制作富集结果气泡图；相关结果采用Cytoscape 3.7.2进行可视化研究及网络拓扑结构分析。结果 筛选得到芍药甘草汤中102种活性成分，对应310个潜在靶点，其中涉及类风湿关节炎靶点68个。药物-成分-关键靶点-信号通路网络图显示山柰酚、槲皮素、柚皮素、芒柄花黄素、异鼠李素等是芍药甘草汤治疗类风湿关节炎的关键成分，前列腺素内环氧化物合成酶2、一氧化氮合酶2、丝裂原活化蛋白激酶14、过氧化物酶体增殖物激活受体γ、白细胞介素-6、肿瘤坏死因子、白细胞介素-1β等是该方治疗类风湿关节炎的关键靶点。GO富集分析显示与生物过程相关的条目28个，与细胞组成相关的条目2个，与分子功能相关的条目13个。通路富集分析显示与40条通路相关，涉及肿瘤坏死因子信号通路、破骨细胞分化、T细胞受体信号通路、MAPK信号通路、类固醇激素生物合成、Toll样受体信号通路等。结论 从网络药理学角度阐明了芍药甘草汤多成分、多靶点、多途径的整体调节特点，初步揭示了芍药甘草汤治疗类风湿关节炎的物质基础和作用机制，为后续研究提供思路与依据。

Objective To study the mechanism of Shaoyao Gancao Decoction in the treatment of rheumatoid arthritis (RA) based on network pharmacology. Methods The active components of Shaoyao Gancao Decoction were obtained from traditional Chinese medicine systems pharmacology (TCMSP) database, and human target proteins corresponding to active components were searched in Swiss Target Prediction and TCMSP database. The targets of RA were collected through Therapeutic Target Database and Drugbank database. The key targets of Shaoyao Gancao Decoction to treat RA were screened by building the Venn diagram. And the key protein interaction (PPI) network model was constructed by STRING database. The gene ontology (GO) and pathway enrichment analysis were performed by DAVID database. All of the correlative results were visualized by Cytoscape 3.7.2, and the network feature analysis was made by Network Analyzer. Results A total of 102 compounds were obtained from Shaoyao Gancao Decoction, with 310 corresponding targets, and 68 common targets of Shaoyao Gancao Decoction-RA were obtained. Herb-compound-target-pathway network showed that kaempferol, quercetin, formononetin, naringenin, isorhamnetin were the key compounds of Shaoyao Gancao Decoction in the treatment of RA, and PTGS2, NOS2, MAPK14, PPARG, IL-6, TNF, and IL-1β were the key targets. GO entries included 28 biological process entries, two cellular component entries, and 13 molecular function entries. There were 40 pathways involving TNF signaling pathway, osteoclast differentiation, T cell receptor signaling pathway, MAPK signaling pathway, steroid hormone biosynthesis and toll-like receptor signaling pathway. Conclusion The results of this study verify the multi-component, multi-target and multi-pathway regulation characteristics of Shaoyao Gancao Decoction, preliminarily predict material basis and mechanism of Shaoyao Gancao Decoction in the treatment of RA, which provides reference for further research.

R285.5

国家重点基础研究发展计划（“973”计划）课题（2009CB522803）；北京中医药大学科研发展基金（2020072120047）