基于网络药理学研究真武汤治疗扩张型心肌病的作用机制  

A study on the mechanism of the Zhenwu decoction in the treatment of dilated cardiomyopathy based on network pharmacology

作　　者：李明阳 曹海明 李峥[2] 李文杰[2] LI Mingyang

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳114001

出　　处：《中医临床研究》2023年第7期15-22,共8页Clinical Journal Of Chinese Medicine

摘　　要：目的:通过网络药理学方法和分子对接技术研究真武汤治疗扩张型心肌病(Dilated Cardiomyopathy,DCM)的作用及其机制。方法:使用中药系统药理学数据库与分析平台(TCSMP)等数据库精选真武汤中药材的主要活性成分和功能靶点,再利用Gene Cards、OMIM等数据库获取DCM的关键靶点,进而筛选出其共同作用靶点。并利用Cytoscape 3.8.2软件来建立“真武汤-有效成分-DCM-靶点”网络图。并通过String数据库获得蛋白质-蛋白质相互作用的网络,从而筛选出了关键基因。利用DAVID数据库对关键靶点做了基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析。利用RCSB PDB、Pub Chem数据库,利用Chem Bio3D、Py MOL以及Auto Dock pyrx内部的Vina软件工具做分子对接,最后使用DS2019软件作图。结果:共得到真武汤中药物主要活性成分59个、重要交集靶点38个,GO富集功能分析显示条目628个,KEGG富集通路126个。真武汤主要活性成分包括β-谷甾醇、山柰酚、常春藤皂苷元等;关键靶点有丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、一氧化氮合酶3(Nitric Oxide Synthase 3,NOS3)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)等;主要涉及癌症途径、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(Advanced Glycation End Product Receptor,RAGE)信号通路、肿瘤坏死因子信号通路等。结论:真武汤可能利用环磷酸鸟苷(Cyclic Guanosine Monophosphate,c GMP)-蛋白激酶G(Protein Kinase G,PKG)、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/Akt信号通路等调控心肌细胞的凋亡与自噬、抑制心肌纤维化,从而对DCM起到明显的治疗作用。Objective:To investigate the mechanism of the Zhenwu decoction(真武汤)in the treatment of dilated cardiomyopathy(DCM)by network pharmacology method and molecular docking technology.Methods:The Trational Chinese Medicine System Pharmacology Analysis Platform(TCSMP)database was used to screen the active components and their targets of the Zhenwu decoction,and map each other to obtain common targets of drugs and diseases.Cytoscape software was used to construct the network diagram of the Zhenwu decoction-ingredient-DCM-target.The String database was used to construct protein protein interaction(PPI)network and screen key genes.GO and KEGG pathway enrichment analysis was performed on key targets through the DAVID database.Molecular docking was performed by the RCSB PDB,PubChem database,PyMOL,ChemBio3D and the Vina software inside the AutoDock pyrx software,and finally the DS2019 software was used for mapping.Results:A total of 59 active ingredients of the Zhenwu decoction were screened,and 38 intersection targets of the Zhenwu decoction in the treatment of dilated cardiomyopathy were identified.The enrichment analysis showed 102 GO items and 152 KEGG pathways.The main active ingredients includeβ-sitosterol,kaempferol,hederagenin,etc..Key targets were AKT1,NOS3,PPARG,etc..It mainly involved cancer pathways,lipids and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,tumor necrosis factor signaling pathway and other pathways.Conclusion:The Zhenwu decoction may regulate myocardial cell apoptosis and autophagy,inhibit myocardial fibrosis and other mechanisms through cGMP-PKG,PI3K/Akt signaling pathways,so as to play a therapeutic role in the treatment of dilated cardiomyopathy.

关 键 词：真武汤 扩张型心肌病 网络药理学 分子对接 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]