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昆明山海棠-鸡血藤药对治疗类风湿关节炎作用机制的网络药理

        学研究        Δ


        刘丹凯 ,王 强 ,魏赈权 ,刘小宝 ,郑雪霞 ,钱 凯 ,曾丽盈 ,许舒迪 ,林昌松 (1.广州中医药大学第一临
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              1*
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        床医学院,广州 510006;2.广州中医药大学第一附属医院风湿病科,广州 510405)
        中图分类号 R593.22         文献标志码 A           文章编号     1001-0408(2019)19-2639-06
        DOI  10.6039/j.issn.1001-0408.2019.19.10
        摘  要   目的:研究昆明山海棠-鸡血藤药对治疗类风湿关节炎的作用机制。方法:通过检索治疗靶点数据库(TTD)、药物银行
       (DrugBank)和DisGeNET数据库获取类风湿关节炎靶点,并构建靶点互作(PPI)网络筛选关键靶点。以口服生物利用度(OB)≥
        30%、类药性(DL)≥0.18、半衰期(HL)≥4 h 为指标,借助中药系统药理学数据库及分析平台(TCMSP)和中药综合数据库(TC-
        MID)获取昆明山海棠-鸡血藤药对的活性成分,并预测其靶点,构建昆明山海棠-鸡血藤药对活性成分-靶点网络;借助 Systems
        Dock Web Site在线平台、Genomics平台筛选昆明山海棠-鸡血藤药对的活性成分和类风湿关节炎的共有靶点,然后利用Cytoscape
        3.2.1软件中Cluego插件分析共有靶点的京都基因与基因组百科全书(KEGG)信号通路。结果:共检索到类风湿关节炎靶点1 956
        个,其中关键靶点11个[包括白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)等];昆明山海棠-鸡血藤药
        对共筛选出30种活性成分(包括木犀草素、芒柄花黄素、β-谷甾醇、雷公藤甲素等)和229个靶点。昆明山海棠-鸡血藤药对和类风
        湿关节炎的共有靶点有37个[包括基质金属蛋白2(MMP2)、TNF、VEGFA等];参与的KEGG信号通路有细胞凋亡、IL-17信号通
        路、Th17细胞分化信号通路、TNF信号通路等。结论:昆明山海棠-鸡血藤药对可能通过MMP2、TNF、VEGFA等靶点作用于细胞
        凋亡、IL-17信号通路等多条信号通路发挥治疗类风湿关节炎的作用,本研究结果可为进一步研究昆明山海棠-鸡血藤药对治疗类
        风湿关节炎的作用机制提供参考。
        关键词 类风湿关节炎;昆明山海棠-鸡血藤药对;网络药理学;作用机制;信号通路

        Network Pharmacology Study on the Mechanism of Couplet Medicine of Tripterygium hypoglaucum-
        Spatholobus suberectus in the Treatment of Rheumatoid Arthritis
        LIU Dankai ,WANG Qiang ,WEI Zhenquan ,LIU Xiaobao ,ZHENG Xuexia ,QIAN Kai ,ZENG Liying ,XU
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        Shudi ,LIN Changsong(1.The First Clinical Medical College,Guangzhou University of TCM,Guangzhou
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        510006,China;2.Dept. of Rheumatology,the First Affiliated Hospital of Guangzhou University of TCM,
        Guangzhou 510405,China)
        ABSTRACT   OBJECTIVE:To study the mechanism of couplet medicine of Tripterygium hypoglaucum-Spatholobus suberectus in
        the treatment of rheumatoid arthritis(RA). METHODS:The RA targets were retrieved and obtained by therapeutic target database
       (TTD),DrugBank and DisGeNET databases,and the protein protein interaction(PPI)network was constructed to screen its key
        targets. Using oral bioavailability(OB)≥30%,drug like(DL)≥0.18 and drug half-life(HL)≥4 h as index,active components
        were obtained from couplet medicine of T. hypoglaucum-S. suberectus by using TCM systematic pharmacological analysis platform
       (TCMSP)and TCM integrated database(TCMID),and the targets were predicted. The active component-target network of couplet
        medicine of T. hypoglaucum-S. suberectus was constructed. Systems Dock Web Site online platform and Genomics platform were
        used to screen the active component and common targets of RA of couplet medicine of T. hypoglaucum-S. suberectus;KEGG
        signaling pathways of common targets were analyzed by using Cluego plug-in unit of Cytoscape 3.2.1 software. RESULTS:Totally
        1 956 RA targets were retrieved,involving 11 key targets [such as IL-6,TNF,VEGFA]. The couplet medicine contained 30 active
        components (including luteolin,erythroxanthin,β-sitosterol and triptolide) and 229 targets. There were 37 common targets for
        couplet medicine of T. hypoglaucum-S. suberectus and RA(including MMP2,TNF,VEGFA). KEGG signaling way involved cell
                                                           apoptosis,IL-17 signaling pathway,Th17 cell differentiation
            Δ 基 金 项 目 :国 家 自 然 科 学 基 金 资 助 项 目(No.81774262,
                                                           pathway and TNF signaling pathway. CONCLUSIONS:The
        No.81573930);广东省自然科学基金资助项目(No.2017A030311009)
                                                           couplet medicine of T. hypoglaucum-S. suberectus may play a
           *硕士研究生。研究方向:中医药防治风湿病。电话:020-
                                                           role in the treatment of RA by acting on cell apoptosis,IL-17
        36598921。E-mail:liushuigaoshan0904@163.com
           # 通信作者:教授,博士生导师。研究方向:中医药防治风湿病。                  signaling pathway and other signaling pathways through
        电话:020-36598921。E- mail:linchs999@163.com          MMP2,TNF,and VEGFA target. The results of this study


        中国药房    2019年第30卷第19期                                             China Pharmacy 2019 Vol. 30 No. 19  ·2639  ·
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