引用本文:付兴前1,郭礼跃2,欧梁2,孔德忠1,龙刚1,杨先宇1.基于数据挖掘和网络药理学的肝肾亏虚型膝骨关节炎的用药规律及机制分析[J].世界中医药,2022,(05):. |
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基于数据挖掘和网络药理学的肝肾亏虚型膝骨关节炎的用药规律及机制分析 |
Analysis of Medication Rule and Mechanism of Knee Osteoarthritis with Liver and Kidney Deficiency Based on Data Mining and Network Pharmacology |
投稿时间:2021-02-25 |
DOI:10.3969/j.issn.1673-7202.2022.05.024 |
中文关键词: 膝骨关节炎 网络药理学 数据挖掘 肝肾亏虚 用药规律 通路 靶点 机制 |
English Keywords:Knee osteoarthritis Network pharmacology Data mining Liver and kidney deficiency Medication rule Pathway Target Mechanism |
基金项目:贵州省中医药管理局课题(QZYY-2019-031);国家级大学生创新创业训练计划项目(201910662);贵州中医药大学2019年度校内项目([2019]27号);贵州中医药大学第二附属医院院内科研项目(GZEFY[2020]2号) |
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中文摘要: |
目的:基于数据挖掘和网络药理学探讨治疗肝肾亏虚型膝骨关节炎的用药规律及其作用机制。方法:通过检索国家知识基础设施数据库(CNKI)近10年治疗肝肾亏虚型膝骨关节炎的方剂,运用中医传承辅助平台建立数据库,利用该软件的熵聚类等算法,总结出治疗肝肾亏虚型膝骨关节炎方剂中的用药频率、核心组合、核心药物模式及归经频率以及得出新方组合。再运用中药系统药理学数据库与分析平台(TCMSP)、基因表达综合(GEO)、STRING、Metascape等数据库及Cytoscape软件对其核心药物靶点与差异表达基因交集进行蛋白质-蛋白质相互作用(PPI)、京都基因和基因组百科全书(KEGG)分析,并构建药物-成分-靶点关系网络图。结果:筛选符合纳入标准的72首方剂所含药物进行频次统计分析,得出频次≥10次的药物有25味,其中使用频次较高的有牛膝、当归、熟地黄;药物的归经以肝、肾、脾经为主;通过系统熵聚类的层次聚类分析挖掘出核心组合药物16个及新处方8首;对核心药物牛膝、当归与熟地黄进行网络药理学分析得到槲皮素、豆甾醇、β-谷甾醇等关键活性成分及靶点176个;膝骨关节炎差异表达基因258个;核心Hub基因为IL-6、MMP9、CXCL8、JUN、VEGFA;KEGG富集分析主要在IL-17、TNF、Toll样受体、核因子κB等信号通路上。结论:治疗肝肾亏虚型膝骨关节炎以补益肝肾、通络止痛为主,其机制可能通过作用IL-6、MMP9等靶点及对IL-17、TNF、Toll样受体、核因子κB等复杂通路的共同干预实现。 |
English Summary: |
To explore the medication rule and mechanism of Chinese medicine prescriptions in the treatment of knee osteoarthritis with liver and kidney deficiency based on data mining and network pharmacology.Methods:China National Knowledge Infrastructure(CNKI) was searched for the prescriptions for the treatment of knee osteoarthritis with liver and kidney deficiency in the last 10 years.Traditional Chinese Medicine Inheritance Support System was used to establish a database and its entropy clustering algorithm was adopted to summarize the drug frequency,core combination,core drug mode and meridian frequency of the prescriptions for the treatment of knee osteoarthritis with liver and kidney deficiency,and to obtain the new prescription combination.Then Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Gene Expression Omnibus(GEO),STRING and Metascape as well as Cytoscape were employed for the intersection of core drug targets and differentially expressed genes and the construction of protein-protein interaction(PPI) network.Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was performed and the drug-component-target network diagram was established.Results:A total of 72 prescriptions that met the inclusion criteria were selected for frequency statistical analysis.It was found that there were 25 Chinese medicinal materials with frequency≥10,among which Radix Achyranthis Bidentatae,Radix Angelicae Sinensis and Radix Rehmanniae Preparata were used more frequently,and they belonged to the liver,kidney and spleen meridians.Sixteen core combination drugs and 8 new prescriptions were excavated by hierarchical cluster analysis of entropy clustering.The network pharmacological analysis of the core Chinese medicinal materials Radix Achyranthis Bidentatae,Radix Angelicae Sinensis and Radix Rehmanniae Preparata showed that there were 176 key active components and targets,such as quercetin,stigmasterol and β-sitosterol,and 258 differentially expressed genes of knee osteoarthritis.The core Hub genes were mainly IL-6,MMP9,CXCL8,JUN and VEGFA in IL-17,TNF,Toll-like receptor and NF-κB signaling pathways based on KEGG enrichment analysis.Conclusion:The treatment of knee osteoarthritis with liver and kidney deficiency focuses on tonifying and replenishing the liver and kidney,dredging collaterals and relieving pain.The mechanism may be achieved by acting on IL-6,MMP9 and other targets and regulating the complex pathways such as IL-17,TNF,Toll-like receptor and NF-κB signaling pathways. |
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