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 achieve the effect of preventing and treating diabetic cardiomyopathy.
作者
郝蕊
郭凤
蒋洁
马洪艳
姚蓝
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)
出处
《药物流行病学杂志》
CAS
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]。
