目的:基于数据挖掘分析益气活血法的高频配伍规律,并通过网络药理学方法研究其核心药物组治疗膝骨关节炎的作用机制.方法:应用Python 3.8.1 编程对中国中医药在线数据库进行智能抓取,分析其配伍规律,以符合支持度≥0.30,置信度≥0.90,提升度≥1.00 的中药为核心药物组,通过中药系统药理学数据库与分析平台(TCMSP)获取核心药物组的主要活性成分,利用PubChem平台、Swiss Target Prediction平台收集药物靶标基因,通过GeneCards及OMIM数据库获得膝骨关节炎相关靶基因,利用Venny数据库获取药物靶点及疾病靶点的交集,采用Cysoscape软件和STRING数据库分析蛋白质-蛋白质相互作用网络,借助DAVID软件对关键靶基因进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路分析,通过Systems Dock Web Site对成分与关键靶标基因进行分子对接验证.结果:以益气活血法中使用频次最高的药对黄芪-当归为核心药物组,并筛选得到 22 个活性成分,涉及 74 个关键靶基因.网络分析结果表明,核心药物组治疗膝骨关节炎的关键靶点为肿瘤坏死因子(Tumor Necrosis Factor,TNF)、Jun原癌基因(Jun Proto-Oncogene,JUN)、白细胞介素(Interleukin,IL)-6、IL-4、IL-1β和趋化因子 2(C-X-C Motif Chemokine Ligand 2,CXCL2)等;GO富集分析主要涉及脂多糖反应、细胞死亡、迁移的正向调节、细胞因子受体结合等生物学过程,KEGG通路中晚期糖基化终末产物(Advanced Glycation End-product,AGE)与其受体(Receptor for Advanced Glycation End Products,RAGE)信号通路、TNF信号通路、IL-17 信号通路与治疗膝骨关节炎密切相关,分子对接显示关键靶点与山柰酚、β-谷甾醇、槲皮苷具有较高亲和力.结论:初步预测了益气活血法核心药物组对膝骨关节炎的基本药理基础及作用机制,益气活血法治疗膝骨关节炎具有多基因参与、多信号通路的特点.
A study on the mechanism of treating knee osteoarthritis by the supplementing Qi and activating blood circulation therapy based on data mining and network pharmacology
Objective:Base on data mining,the high frequency compatibility of the supplementing Qi(气)and activating blood circulation therapy was analyzed,and the mechanism of its core drug group in the treatment of knee osteoarthritis was studied by the method of network pharmacology.Methods:The online database of TCM was intelligently crawled by Python 3.8.1 programming,and its compatibility rule was analyzed.Taking the TCM with support≥0.30,confidence≥0.90,and lift≥1.00 as the core drug group,the main active components of the core drug group were obtained by TCMSP platform,drug target genes were collected by PubChem platform and Swiss Target Prediction platform,and knee osteoarthritis related target genes were obtained by GeneCards and OMIM database.The intersection of drug target and disease target was obtained by Venny database.The protein interaction network was analyzed by Cysoscape software and STRING database.The key target genes were analyzed by GO analysis and KEGG pathway analysis with DAVID software.The molecular docking between the components and key target genes was verified by Systems Dock Web Site.Results:Huangqi(Radix Astragali)-Danggui(Radix Angelicae Sinensis),which is the most frequently used drug in the supplementing Qi and activating blood circulation therapy circulation,was used as the core drug group,and 22 active components of the core drug group were screened,involving 74 key target genes.The results of network analysis showed that the key targets of the core drug group in the treatment of knee osteoarthritis were TNF,JUN,IL-6,IL-4,IL-1β and CXCL2.GO enrichment analysis mainly involves lipopolysaccharide response,cell death,positive regulation of migration,cytokine receptor binding and so on.AGE-RAGE signal pathway,TNF signal pathway and IL-17 signal pathway in KEGG pathway are closely related to the treatment of knee osteoarthritis.Molecular docking shows that the key targets have high affinity with kaempferol,β-sitosterol and quercitrin.Conclusion:The basic pharmacological basis and mechanism of the core drug combination of the supplementing Qi and activating blood circulation therapy on knee osteoarthritis were preliminarily predicted.The supplementing Qi and activating blood circulation therapy has the characteristics of multi-gene participation and multi-signal pathway in the treatment of knee osteoarthritis.
Supplementing Qi and activating blood circulationKnee osteoarthritisHuangqiDangguiData miningNetwork pharmacology
万方数据
维普
