基于数据挖掘、网络药理学方法和分子对接技术探讨中医药治疗慢性肾脏病的核心中药及作用机制

Exploration of the core Chinese herbs in the treatment of chronic kidney disease and its mechanism based on data mining,network pharmacology and molecular docking technology

目的:通过数据挖掘探讨中药复方治疗慢性肾脏病(chronic kidney disease,CKD)的用药规律,基于网络药理学和分子对接技术对核心中药治疗CKD的作用机制进行分析。方法:从中国知网、维普中文期刊数据库、万方数据知识服务平台获取运用中药复方治疗CKD的文献,运用Excel、SPSS Modeler 18.0、IBM SPSS Statistics 26软件分别进行中药频次统计、关联规则分析和聚类分析,筛选核心中药;检索TCMSP、OMIM等数据库获得核心中药的活性成分及作用靶点、疾病靶点,上传药物与疾病交集靶点至STRING在线平台,构建共同靶点蛋白质互作网络;运用AutoDock Tools 1.5.7软件对核心成分与靶点进行分子对接。结果:检索获得119首处方,涉及194味中药,17味中药使用频次≥20次,核心药物为黄芪、白术、茯苓、党参、大黄、川芎。对使用频次≥20次的中药进行聚类分析,可聚为3类,第1类:黄芪、甘草、山药、党参、茯苓、土茯苓;第2类:熟地黄、当归、生地黄、菟丝子、山茱萸、淫羊藿;第3类:半夏、白术、大黄、川芎、丹参。对度值排名靠前的药物活性成分β-谷甾醇(beta-sitosterol)、肉豆蔻酮(myricanone)、槲皮素(quercetin)、常春藤皂苷元(hederagenin)、3β-乙酰氧基苍术酮(3β-acetoxyatractylone)、木犀草素(luteolin)与关键靶点VEGFA、TP53、IL6、JUN、TNF进行分子对接,其中,槲皮素与TNF结合最稳定,其次为槲皮素与IL6,槲皮素、木犀草素来自于黄芪、党参。结论:中药复方治疗CKD以健脾补肾为本,活血、除湿、泄浊治其标为原则。核心药物可能是通过调控炎症、肾脏纤维化等信号通路,作用于VEGFA、IL6、TNF等靶点发挥治疗作用。

Objective:To explore the medication rules of traditional Chinese medicine compound in the treatment of chronic kidney disease(CKD)through data mining,and to analyze the mechanism of core Chinese herbs in the treatment of CKD based on network pharmacology and molecular docking technology.Methods:Literature on the treatment of CKD with traditional Chinese medicine compound was obtained from CNKI,VIP Chinese periodical database and Wanfang data knowledge service platform.Excel,SPSS Modeler 18.0 and IBM SPSS Statistics 26 were used to conduct frequency statistics of Chinese herbs,association rule analysis and cluster analysis,and select core Chinese herbs.The active ingredients,targets of core Chinese herbs and disease targets were obtained by searching TCMSP,OMIM and other databases.The intersection targets of drugs and diseases were uploaded to the STRING online platform to construct a common target protein interaction network.AutoDockTools 1.5.7 software was used for molecular docking of core components and targets.Results:119 prescriptions were obtained,involving 194 Chinese herbs,among which 17 Chinese herbs were used more than 20 times.The core drugs were Huangqi,Baizhu,Fuling,Dangshen,Dahuang and Chuanxiong.By cluster analysis,the Chinese herbs used more than 20 times could be clustered into 3 categories.The first category:Huangqi,Gancao,Shanyao,Dangshen,Fuling,and Tufuling.The second category:Shudi,Danggui,Shengdi,Tusizi,Shanzhuyu,and Yinyanghuo.The third category:Banxia,Baizhu,Dahuang,Chuanxiong,and Danshen.The active ingredients with the top degree value were beta-sitosterol,myricanone,quercetin,hederagenin,and 3β-acetoxyatractylon,and luteolin.They performed molecular docking with key targets of VEGFA,TP53,IL6,JUN and TNF.Quercetin and TNF were the most stable binding,followed by quercetin and IL6.Quercetin and luteolin were derived from Huangqi and Dangshen.Conclusion:The treatment of CKD by traditional Chinese medicine compound is based on fortifying spleen and tonifying kidney,and the principles of invigorating blood,eliminating dampness and removing turbidity to treat the manifestations.Core drugs may exert therapeutic effects on VEGFA,IL6,TNF and other targets by regulating signaling pathways such as inflammation and renal fibrosis.