基于网络药理学研究艾迪注射液治疗肝细胞癌的作用机制  

Mechanism of Aidi injection on hepatocellular carcinoma based on network pharmacology

作　　者：丁园园 张冬华[1] 张荣生[1] 张沥元 郭程昊 王轩[1] DING Yuan-yuan;ZHANG Dong-hua;ZHANG Rong-sheng;ZHANG Li-yuan;GUO Cheng-hao;WANG Xuan(Affiliated 81st Hospital of University of Chinese Medicine,Nanjing 210002,China)

机构地区：[1]南京中医药大学附属八一医院,江苏南京210002

出　　处：《海南医学院学报》2020年第8期602-610,共9页Journal of Hainan Medical University

基　　金：南京军区医学科技创新课题(14ZX07)。

摘　　要：目的:利用网络药理学方法探索艾迪注射液治疗肝细胞癌的活性成分及潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)和中药综合数据库(TCMID)筛选艾迪注射液中人参、黄芪、刺五加、斑蝥四味中药的活性成分及对应潜在靶点。通过人类孟德尔遗传数据库(OMIM)和GeneCards Suite数据库平台筛选肝细胞癌相关靶点。将药物和疾病靶点合并取其交集,将信息导入Cytoscape 3.7.2构建艾迪注射液活性成分和肝细胞癌相关靶点的网络图,同时进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用(protein-protein interaction,PPI)网络并进行分析。运用生物信息注释数据库(DAVID)对靶点进行GO功能和KEGG通路富集分析。结果:艾迪注射液中共筛选出33个活性成分,包括槲皮素(quercetin)、山奈酚(kaempferol)、β-谷甾醇(beta-sitosterol)、异鼠李素(isorhamnetin)等,其对应靶点106个,疾病相关靶点6677个,药物-疾病共同靶点89个。网络图发现度值最高的靶点是环加氧酶1(PTGS1);PPI图的87个节点中度值较高的关键靶点包括白细胞介素6(IL-6)、半胱氨酸蛋白酶3(CASP3)、血管内皮生长因子A(VEGFA)、丝裂原激活蛋白激酶8(MAPK8)、氨基端激酶c-Jun(JUN)、表皮生长因子受体(EGFR)、原癌基因(MYC)、环加氧酶2(PTGS2)、原癌基因c-Fos(FOS)等。GO富集分析共获得60条相关信号通路,主要涉及抑制肝癌细胞异常增殖、分化,抑制肝癌血管生成,调控细胞周期,促进细胞凋亡等生物学过程。KEGG通路富集分析共筛选获得8条存在显著差异的信号通路,其中P53、VEGF、MAPK、Toll样受体、ErbB等信号通路在治疗中发挥重要作用。结论:本研究初步揭示了艾迪注射液治疗肝细胞癌的多成分、多靶点、多通路的潜在作用机制,为后续验证艾迪注射液治疗肝细胞癌的分子机制提供了思路。Objective To explore the active ingredients and potential mechanism of Aidi injection in the treatment of hepatocellular carcinoma by network pharmacology.MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID)were used to screen the active ingredients of four traditional Chinese medicines of Renshen,Huangqi,Ciwujia,and Banmao and corresponding potential targets.Screening of hepatocellular carcinoma-related targets through the Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database platforms was conducted.The drug and disease targets were merged to obtain the intersection,and the information was imported into Cytoscape 3.7.2 to construct a network diagram of the active ingredients of Aidi injection and related targets of hepatocellular carcinoma,and the topology analysis is performed.A protein-protein interaction(PPI)network was constructed and analyzed using the STRING online analysis platform.The study utilized the database for annotation,visualization and integrated discovery(DAVID)to perform GO function enrichment analysis of targets and enrichment of KEGG pathways analysis.Results A total of 33 potential active ingredients were screened from Aidi injection for treating hepatocellular carcinoma,including quercetin,kaempferol,beta-sitosterol,isorhamnetin and other important active ingredients.There are 106 potential targets for active ingredient action,6677 disease-related targets,and 89 drug-disease common targets.Through the network diagram,it was found that the highest degree of target is PTGS1.In the PPI graph,a total of 87 nodes.Among them,the higher degree values include IL6,CASP3,VEGFA,MAPK8,JUN,EGFR,MYC,PTGS2 and FOS.A total of 60 related signal pathways were obtained by GO enrichment analysis.It mainly involves biological processes such as inhibiting abnormal proliferation and differentiation of hepatocellular carcinoma cells,inhibiting angiogenesis of hepatocellular

关 键 词：网络药理学 艾迪注射液 肝细胞癌 作用机制 

分 类 号：R285[医药卫生—中药学]