综合生物信息学分析马兜铃致急性肾损伤作用机制的研究  

Study on the Mechanism of Aristolochia Induced Acute Kidney Injury by Comprehensive Bioinformatics Analysis

作　　者：陈锋斌[1] 赖坤美 陈志敏 阮诗玮[3] 张鹤 许艳芳[2] CHEN Fengbin;LAI Kunmei;CHEN Zhimin;RUAN Shiwei;ZHANG He;XU Yanfang(Department of Traditional Chinese Medicine,the First Affiliated Hospital of Fujian Medical University,Fuzhou Fujian 350005,China;Department of Nephrology,the First Affiliated Hospital of Fujian Medical University/Blood Purification Research Center/Fujian Clinical Research Center for Metabolic Chronic Kidney Disease,Fuzhou Fujian 350005,China;Department of Nephrology,Fujian Provincial People's Hospital,Fuzhou Fujian 350005,China;Medical Records Room,National Regional Medical Center/Binhai Campus,the First Affiliated Hospital of Fujian Medical University,Fuzhou Fujian 350212,China)

机构地区：[1]福建医科大学附属第一医院中医科,福建福州350005 [2]福建医科大学附属第一医院肾内科/血液净化研究中心/福建省代谢性慢性肾脏病临床研究中心,福建福州350005 [3]福建省人民医院肾内科,福建福州350005 [4]国家区域医疗中心/福建医科大学附属第一医院滨海院区病案室,福建福州350212

出　　处：《中国卫生标准管理》2025年第2期141-146,共6页China Health Standard Management

基　　金：2020年福建省卫生健康青年科研课题资助项目(2020QNA043)。

摘　　要：目的基于网络药理学和分子对接技术探讨马兜铃致急性肾损伤(acute kidney injury,AKI)的作用机制。方法2022年,通过查询中药系统药理学数据库及分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获取马兜铃活性成分,在蛋白质资源(universal protein,UniProt)数据库和瑞士目标预测(Swiss target prediction,Swiss)数据库检索马兜铃活性成分的预测靶标,在人类基因数据库(the human gene database,GeneCards)和人类疾病相关的基因与突变位点信息的数据库(diseaseassociated genes and variants,DisGeNET)检索得到AKI相关靶点;利用Cytoscape软件构建“药物-活性成分-靶点-AKI”的复杂关系网络;借助基因、蛋白质相互作用关系检索工具(search tool for the retrieval of interacting genes/proteins,STRING)平台进一步绘制蛋白质之间的相互作用关系网络;利用R软件对共有靶点基因功能进行富集分析;利用分子对接进行半柔性对接反向验证。结果共得到马兜铃活性成分9个、靶点292个,AKI作用靶点734个,映射后得到马兜铃致AKI潜在靶点84个;马兜铃“成分-靶点-疾病”相互作用关系网络和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集表明马兜铃致AKI是基于多成分、多基因、多靶点的协同复杂作用;分子对接结果表明由马兜铃中筛选出的活性成分与对应的蛋白靶点具有良好的结合能力。结论马兜铃不仅调节脂质代谢、内分泌代谢通路,还可以通过调节衰老、肿瘤等通路影响AKI进程。Objective To explore the the mechanism of aristolochia induced acute kidney injury(AKI)based on network pharmacology and molecular docking method.Methods In 2022,the active components of aristolochia were searched by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).The predicted targets of the active components of aristolochia were retrieved from universal protein(UniProt)database and Swiss target prediction(Swiss)database,and the targets related to AKI were retrieved from the human gene database(GeneCards)and disease-associated genes and variants(DisGeNET).The complex relationship network of"drug-active ingredient-target-AKI"was constructed using Cytoscape software.The interaction network among proteins was further mapped with the search tool for the retrieval of interacting genes/proteins(STRING)platform.Using R software,the common targets were enriched and analyzed by functional genomics.Reverse verification of semi flexible docking was carried out by molecular docking.Results A total of 9 active components of aristolochia,292 targets and 734 targets of AKI were obtained.After mapping,84 potential targets of AKI caused by aristolochia were obtained.The"composition-target-disease"interaction network of aristolochia and the enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway indicate that AKI caused by aristolochia was based on the synergistic complex effects of multi-components,multi-genes and multi-targets.The results of molecular docking showed that the active components screened from aristolochia had good binding ability with the corresponding protein targets.Conclusion Aristolochia not only regulates lipid metabolism,endocrine and metabolic pathways,but also regulates aging,tumor and other pathways to affect the progression of AKI.

关 键 词：马兜铃 急性肾损伤 中药 网络药理学 分子对接 作用机制 

分 类 号：R692[医药卫生—泌尿科学]