基于数据挖掘和网络药理学探讨中医药治疗糖尿病性勃起功能障碍的机制

Exploring the action mechanism of treating diabetes mellitus-induced erectile dysfunction in TCM based on data mining and network pharmacology

目的:基于数据挖掘和网络药理学分析中医药治疗糖尿病性勃起功能障碍(Diabetes Mellitus-induced Erectile Dysfunction,DMED)的用药规律及作用机制。方法:检索中文数据库中中医药治疗DMED的文献,建立DMED处方信息数据库,运用EXCEL、SPSS Modeler 18软件进行数据挖掘,分析DMED的用药规律,并筛选出核心药物组合。通过中药系统药理学数据库与分析平台(TCMSP)获取核心药物组合的活性成分,运用本草组鉴预测药物作用靶点;运用Gene Cards、OMIM及Dis Genet数据库预测疾病相关靶点;运用Venny平台得到疾病与药物的交集靶点;运用Cytoscape建立“活性成分-靶点”网络,筛选出关键成分;以STRING平台数据为基础,利用Cytoscape软件构建蛋白质-蛋白质相互作用网络,筛选核心靶点;通过DAVID数据库对交集靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析;采用Auto Dock Vina进行分子对接。结果:共纳入文献104篇,提取出方剂135首,涉及药物191味,药物性味归经以性温、味甘、归肝经和肾经为主。筛选出菟丝子-山药-熟地黄为核心药物组合,涉及21个活性成分、235个药物作用靶点,与DMED有143个交集靶点;槲皮素、山柰酚、β-谷甾醇等为关键成分,肿瘤蛋白p53(Tumor Protein p53,TP53)、Jun原癌基因(JUN)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)3等为核心靶点;GO分析得到生物过程718条、细胞组成85项、分子功能135项;KEGG分析显示核心药物组合主要通过调控癌症通路、脂质与动脉粥样硬化、糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)信号通路治疗DMED。分子对接结果显示,核心靶点与关键成分结合能均小于-5 kcal/mol,两者具有良好的亲和力。结论:养阴生津止渴、益肾固精填髓是DMED主要治法;核心药物组合通过多成分、多靶点、多通路治疗DMED,为临床治疗及优化用药提供依据与参考。

Objective:A study was conducted to explore the medication rules and potential mechanism of TCM medicine in treating diabetes mellitus-induced erectile dysfunction based on data mining and network pharmacology.Methods:The prescription information database of DMED was established by retrieving the literature of TCM medicine in the treatment of DMED in the Chinese database.Using EXCEL and SPSS Modeler 18 for data mining,the medication rules of DMED were analyzed,and the core drug combinations were screened.The active components of core drug combinations were obtained by TCMSP database,and HERB database was used to predict drug targets.The disease targets were predicted in GeneCards,OMIM and DisGenet databases.The Venny platform was used to obtain the intersection targets of diseases and drugs.Key components were screened by Cytoscape to establish a active component-target network.Based on STRING platform data,PPI network was constructed by Cytoscape to screen core targets.GO and KEGG analyses were performed on the intersection targets by DAVID.AutoDockVina was used for molecular docking.Results:A total of 104 articles were included,and 135 prescriptions involving 191 Chinese materia were extracted.The nature and taste of drugs were mainly warm,sweet,and the main components of the drug flowed mainly into liver and kidney meridians.Tusizi(Semen Cuscutae)-Shanyao(Rhizoma Dioscoreae)-Shudihuang(Radix Rehmanniae Praeparata)was screened as the core drug combination involving 21 active components,235 drug action targets and 143 intersection targets with DMED.Quercetin,kaempferol andβ-sitosterol were the key components,and TP53,JUN and MAPK3 were the core targets.GO analysis revealed 718 biological processes,85 cellular components and 135 molecular functions.KEGG analysis showed that the core drug combination was mainly used to treat DMED by regulating pathways in cancer,lipid and atherosclerosis,and AGE-RAGE signaling pathway in diabetic complications.Molecular docking results showed that the binding energies of the core target and the key components were both less than-5 kcal/mol,and there was a good affinity between the core target and the key component.Conclusion:Nourishing Yin(阴),promoting body fluid,quenching thirst,tonifying kidney,strengthening essence and filling marrow are the main treatment methods of DMED.Core drug combinations treat DMED through multi-component,multi-target and multi-pathway,which provide a basis and reference for clinical treatment and optimization of drug use.