姚卓汝 刘红波 唐志书 宋忠兴 阮凯华 徐思宁 于金高 刘世军

摘要 目的：基于網络药理学探讨秦七风湿方（QQFSF）治疗类风湿性关节炎（RA）的物质基础及其作用机制。方法：通过中医百科全书数据库（ETCM）检索QQFSF中珠子参、秦艽、山茱萸3味中药的成分和靶点;从NCBI、Geencards数据库中检索RA的相关靶点，将QQFSF治疗RA的靶点通过蛋白质-蛋白质相互作用（PPI）网络分析及DAVID进行功能通路富集分析，预测其作用机制。运用Cyoscape 3.7.2软件构建“中药-成分-靶点-通路”网络，经拓扑学分析得到核心成分和靶点。结果：从QQFSF筛选出成分122个，其中有靶点的成分84个，共筛选到靶点420个。检索得到RA的靶点1 225个。经映射分析，获得成分与疾病的共同靶点72个。通过对网络进行拓扑分析，得到熊果酸、齐墩果酸等核心成分及ABCB1、ABCC1、PIK3CG等核心靶点。经DAVID（P<0.05）富集分析，得到62条信号通路。最后通过分子对接技术对核心成分及靶点进行验证。结论：QQFSF治疗RA的主要成分是熊果酸、齐墩果酸、棕榈酸，靶点主要涉及ABCG2、ABCB1、PIK3CG等，并通过甲状腺激素信号通路、胰岛素抵抗、核因子κB信号通路等达到治疗RA的作用。

关键词 秦七风湿方;类风湿性关节炎;网络药理学;分子对接;作用机制

Mechanism of Qinqi Fengshi Formula for the Treatment of Rheumatoid Arthritis by Network Pharmacology

YAO Zhuoru1，2，LIU Hongbo1，2，TANG Zhishu1，2，SONG Zhongxing1，2，RUAN Kaihua1，2，XU Sining1，2，YU Jingao1，2，LIU Shijun1，2

（1 Shaanxi University of Chinese Medicine/Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization，Xianyang 712083，China; 2 State Key Laboratory of Research and Development of Characteristic Resources of Qin Medicine（Cultivation）/Shaanxi Provincial Innovative Medicine Research Center，Xianyang 712083，China）

Abstract Objective：To explore the material basis and mechanism of Qinqi Fengshi Formula（QQFSF） in the treatment of rheumatoid arthritis（RA） based on network pharmacology.Methods：ETCM databases was used to search the components and targets of 3 Chinese medicinals，namely，Panacis Majoris rhizome，Gentianae Macrophyllae Radix，and Corni Fructus in QQFSF.The related targets of RA were retrieved from NCBI and Geencards databases.The target of QQFSF in the treatment of RA was analyzed by PPI network analysis and DAVID for functional pathway enrichment analysis to predict its mechanism of action.The “Chinese medicine-component-target-pathway” network was constructed by Cytoscape 3.7.2 software.Through the topology analysis，the core components and targets were obtained.Results：A total of 122 components in QQFSF were screened，among which 84 components with targets were selected，and 420 targets were screened.A total of 1 225 targets of RA were retrieved.Through mapping analysis，72 common targets of components and diseases were obtained.A total of 1 225 RA targets were retrieved.After mapping analysis，72 common targets of ingredients and diseases were obtained.Through topological analysis of the network，core components such as ursolic acid and oleanolic acid and core components and ABCB1，ABCC1 and PIK3CG and other targets were obtained（P<0.05）.After DAVID（P<0.05） enrichment analysis，62 signal pathways were obtained.Finally，the core components and targets were verified by molecular docking technology.Conclusion：The main therapeutic components of QQFSF for RA are ursolic acid，olenolic acid and palmitic acid.The targets mainly involve ABCG2，ABCB1，PIK3CG，etc.，and its therapeutic effect is achieved through thyroid hormone signaling pathway，insulin resistance and NF-κB signaling pathway etc.for the treatment of RA.

Keywords Qinqi Fengshi Formula; Rheumatoid arthritis; Network pharmacology; Molecular docking; Action mechanism

中图分类号：R285.5;R289.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.16.005

类风湿性关节炎（Rheumatoid Arthritis，RA）是一种以关节滑膜炎为特征的慢性自身免疫性疾病[1]。目前临床治疗RA以化学药物为主，常用药物有非甾体抗炎药（NSAIDs）、水杨酸类药物、糖皮质激素及免疫制剂等[2-4]。化学药物治疗RA的短期疗效较为显著，但其作用靶点单一，对疾病的整体调控有限;同时长期使用往往会产生胃肠道、肝脏、肾等组织的诸多不良反应[5-6]。近年来，中药治疗RA的研究较多[7-9]。相比于化学药物，中药多成分、多靶点、多通路的整体治疗特点使其在RA治疗方法具有独特的优势。

组方来源于陕西太白“七”药的秦七风湿方（QQFSF）由珠子参、秦艽、山茱萸3味中药组成，是治疗RA的临床经验方，具有散寒除湿、益气养阴、祛风止痛等功效。……