丹参-黄芪调节自噬防治糖尿病心肌病的lncRNA-miRNA-mRNA转录网络研究  

The lncRNA-miRNA-mRNA transcription network of the Salvia miltiorrhixa Bge-Hedysarum multijugum Maxim in preventing and treating diabetic cardiomyopathy by regulating autophagy

作　　者：郝蕊 郭凤 蒋洁[2] 马洪艳[2] 姚蓝[2] Rui HAO;Feng GUO;Jie JIANG;Hong-Yan MA;Lan YAO(Affiliated Hospital of Traditional Chinese and Western Medicine Nanjing University of Traditional Chinese Medicine,Nanjing 210046,China;College of Traditional Chinese Medicine of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]南京中医药大学附属中西医结合医院,南京210046 [2]新疆医科大学中医学院,乌鲁木齐830011

出　　处：《药物流行病学杂志》2023年第10期1113-1126,共14页Chinese Journal of Pharmacoepidemiology

基　　金：新疆维吾尔自治区天山英才计划第三期(2021241);新疆维吾尔自治区“十四五”重点学科-中西结合临床医学项目[(2022)112]。

摘　　要：目的 基于网络药理学与生物信息学技术探讨丹参-黄芪调节自噬防治糖尿病心肌病(DCM)的活性成分及构建长链非编码RNA(lncRNA)-微小RNA(miRNA)-信使RNA(mRNA)转录网络。方法 利用TCMSP数据库检索丹参-黄芪的化学成分及靶点;通过CTD、GeneCards数据库筛选获得DCM和自噬的相关靶点;STRING数据库构建蛋白质-蛋白质相互作用网络并进行网络拓扑分析;通过Cytoscape软件中的Hubba插件5种算法筛选核心靶点;通过Metascape数据库对靶点进行基因本体和京都基因与基因组百科全书富集分析;利用微生信平台构建中药核心成分-核心靶点-核心信号通路网络;用Discovery Studio Client 19.1.0软件进行分子对接;用Target Scan Human、miRDB、miRTarBase数据库预测靶点mRNA上游调控的miRNAs并筛选核心miRNA;StarBase数据库预测miRNA竞争性结合的lncRNAs并筛选得到核心lnc RNA,构建竞争性内源RNA网络。结果 丹参-黄芪中调节自噬防治DCM的活性成分为丹酚酸J、丹参酮ⅡB、丹参二醇A、黄芪异黄烷苷等;其核心靶点为原癌基因、生长因子受体结合蛋白2等;核心通路为磷酯酰肌醇3激酶/蛋白激酶B、叉头转录因子、晚期糖基化终末产物-晚期糖基化终末产物受体等;基于核心靶点m RNA预测的核心miRNA为miR-4731-5p、miR-503-5p等12个;核心lncRNA为NEAT1、XIST等5个。结论 丹参-黄芪可能通过调节自噬影响细胞凋亡、氧化应激、糖代谢等过程协同发挥作用,从而达到防治DCM的作用。Objectives To study the active components and targets of Salvia miltiorrhixa Bge-Hedysarum multijugum Maxim in the treatment of diabetic cardiomyopathy based on network pharmacology and bioinformatics technology,and to construct lncRNAmiRNA-mRNA transcription network.Methods The TCMSP database was used to retrieve the chemical constituents and targets of Salvia miltiorrhixa Bge-Hedysarum multijugum Maxim;diabetic cardiomyopathy and autophagy related targets were obtained through CTD and GeneCards database screening;protein-protein interaction network was constructed through STRING database and the core targets were screened by five algorithms for the Hubba plugin in Cytoscape software;the gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of the targets were carried out through the Metascape database;the core componentcore targets-core signaling pathway network were constructed used bioinformatic platform;Discovery Studio Client 19.1.0 software was used for molecular docking;the miRNAs regulated upstream of target mRNA was predicted and the core miRNAs was screened through Target Scan Human,miRDB and miRTarBase databases;StarBase database was used to predict lncRNAs with miRNA competitive binding,and to screen the core lncRNA,and to construct competitive endogenous RNA network.Results The active ingredients in Salvia miltiorrhixa Bge-Hedysarum multijugum Maxim that regulate autophagy and prevent diabetic cardiomyopathy were salvianolic acid J,tanshinoneⅡB,tanshindiol A and Isomucronulatol 7-O-glucoside,etc;its core targets included SRC and GRB2,etc;the core pathways included PI3K/AKT,FoxO and AGE-RAGE signaling pathways,etc;12 miRNAs related to core targets were screened,including miR-4731-5p and miR-503-5p,etc;there were five core lncRNAs,including NEAT1 and XIST,etc.Conclusions The Salvia miltiorrhixa Bge-Hedysarum multijugum Maxim may exert synergistic effects through regulating autophagy,which can affect processes such as cell apoptosis,oxidative stress,and glucose metabolism,and

关 键 词：长链非编码RNA-微小RNA-信使RNA网络 丹参-黄芪 自噬 糖尿病心肌病 

分 类 号：R285[医药卫生—中药学]