基于网络药理学分析参附苓桂术甘汤加减治疗缺血性心肌病的药理过程和分子机制  

Study on the Pharmacological Processes and Molecular Mechanism of Modified Shenfu Linggui Zhugan Decoction in the Treatment of Ischemic Cardiomyopathy Based on Network Pharmacology

作　　者：全无瑕 缪延栋 QUAN Wuxia;MIAO Yandong(Qingyang People′s Hospital,Qingyang 745000,Gansu,China;The First Clinical Medical College of Lanzhou University,Lanzhou 730000,Gansu,China)

机构地区：[1]庆阳市人民医院,甘肃庆阳745000 [2]兰州大学第一临床医学院,兰州730000

出　　处：《中西医结合心脑血管病杂志》2021年第21期3645-3653,共9页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：庆阳市科技计划资助项目(No.QY2021A-S023)。

摘　　要：目的分析参附苓桂术甘汤加减治疗缺血性心肌病(ICM)的药理过程和分子机制。方法通过GEO数据库筛选出ICM差异表达基因。中药系统药理学分析平台(TCMSP)检索参附苓桂术甘汤加减方中8味中药所含的化学成分及作用靶点。采用Cytoscape软件构建“中药有效活性成分-靶点”网络。通过Bisogenet插件构建靶点间的蛋白互作(PPI)网络,CytoNCA插件筛选出核心基因,最后运用基因本体(GO)功能注释及京都基因与基因组百科全书(KEGG)通路分析,明确靶点基因的功能及参与调控的信号转导通路。结果筛选出20个生物活性成分和11个靶点,在PPI网络中共筛选出19个核心基因,HSP90AA1、CDKN1A、POR、MYC、GJA1、CCL2、SERPINE1、COL1A1、COL3A1、PCOLCE、ADH1B为核心靶基因,靶点主要富集在DNA合成过程的调控、细胞外基质等生物学过程,主要参与磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)、p53、低氧诱导因子-1(HIF-1)和细胞周期等信号通路的调控过程,产生保护心肌细胞、减轻心室重构等作用,进而发挥改善心脏功能的作用。结论参附汤合苓桂术甘汤通过多种活性成分作用于靶点基因调控相关信号转导通路,从而治疗ICM。Objective To explore the pharmacological process and molecular mechanism of modified Shenfu Linggui Zhugan decoction in the treatment of ischemic cardiomyopathy(ICM).Methods The differentially expressed genes of ICM were screened by GEO database.The compounds and action targets of eight herbal medicines of Shenfu Linggui Zhugan decoction were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The"traditional Chinese medicine(TCM)-active ingredient-target"network was constructed by Cytoscape software.The protein interaction network between targets was constructed by Bisogenet plug-in.Finally,gene ontology functional annotation and Kyoto encyclopedia of genes and genomes pathway analysis were used to clarify the function of target genes and signal transduction pathways involved in regulation.Results The composite network contained 20 bioactive components and 11 targets,and 19 core genes were obtained in protein-protein interaction network.HSP90AA1,CDKN1A,POR,MYC,GJA1,CCL2,SERPINE1,COL1A1,COL3A1,PCOLCE,and ADH1B were identified as the most critical core target genes.The targets were mainly concentrated in biological processes such as the regulation of DNA synthesis and extracellular matrix,mainly participated in the regulation of signal pathways such as PI3K-Akt,p53,hypoxia-inducible factor-1,and cell cycle,which could protect cardiomyocytes,reduce ventricular remodeling,and thus improve cardiac function.Conclusion Shenfu Linggui Zhugan decoction treat ICM by a variety of active components acting on target gene regulation-related signal transduction pathways.

关 键 词：缺血性心肌病 参附苓桂术甘汤 网络药理学 中药 作用机制 低氧诱导因子-1 

分 类 号：R73[医药卫生—肿瘤]