基于网络药理学探讨异功散治疗支气管哮喘作用机制  

Mechanism of Yigong San Prescription in Treating Bronchial Asthma Based on Network Pharmacology

作　　者：林晓杰 刘文导[1] 曾丽盈 王伟荣[1] 孙少丹 陈晓刚[2] 陈全福[1] LIN Xiaojie;LIU Wendao;ZENG Liying;WANG Weirong;SUN Shaodan;CHEN Xiaogang;CHEN Quanfu(Department of Medical Affairs,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou Guangdong 510120,China;Department of Pediatrics,The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510405,China;Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510006,China)

机构地区：[1]广东省中医院医务处,广东广州510120 [2]广州中医药大学第一附属医院儿科,广东广州510405 [3]广州中医药大学,广东广州510006

出　　处：《新中医》2024年第7期56-65,共10页New Chinese Medicine

基　　金：第五批全国中医临床优秀人才研修项目(02031302);广东省自然科学基金项目(2017A030313788)。

摘　　要：目的:运用网络药理学、分子对接探讨异功散治疗支气管哮喘(BA)作用机制。方法:通过BATMAN-TCM、中医药百科全书(ETCM)平台、SymMap、TCMDatabase@Taiwan、中药系统药理学数据库和分析平台(TCMSP)获取异功散各药物的潜在活性成分及对应靶点;利用DisGeNET、TTD、GeneCards、PharmGkb、在线人类孟德尔遗传数据库(OMIM)、NCBI、人类表型本体(HPO)和Drugbank数据库收集BA疾病作用靶点,使用Bioinformatics&Evolutionary Genomics平台筛选药物与疾病共有靶点;利用GEO下载基因芯片,使用R语言分析获取差异表达基因,通过药物与疾病共有靶点基因交叉验证获得关键靶点,构建“活性成分-关键靶点”网络;使用R软件对关键靶点进行基因本体论(GO)生物功能分析和京都基因和基因组百科全书(KEGG)通路富集分析;采用STRING数据库和Cytoscape软件获得关键靶点蛋白相互作用关系,筛选出核心靶点;通过AutoDock软件进行核心靶点与活性成分的分子对接验证。结果:共筛选176个药物活性成分及其对应的作用靶点265个,获得差异基因1 263个,交叉验证得到原癌基因1 (PIM1)、人肾上腺素能受体β2 (ADRβ2)、V-rel网状内皮细胞病毒癌基因同源物A (RELA)、碳酸酐酶2 (CA2)基因、肿瘤坏死因子(TNF)等16个关键靶点,关联的活性成分有槲皮素、甘草查尔酮A、甘草查尔酮B、山柰酚、柚皮素等。异功散治疗BA的关键靶点主要富集通路有NOD样受体信号通路、C型凝集素受体信号通路、TNF信号通路等。分子对接结果显示,TNF、RELA、白细胞介素1A (IL1A)、连环蛋白β1 (CTNNβ1)、螺旋环螺旋结构域扩散激酶(CHUK)、CXC型趋化因子配体2 (CXCL2)、磷酸酶-张力蛋白基因(PTEN)、信号转导子和转录激活子1 (STAT1)等核心靶点与槲皮素、甘草查尔酮A、甘草查尔酮B、山柰酚、柚皮素等活性成分均具有良好的结合能力。结论:异功散中槲皮素、甘草查尔酮A、甘草Objective:To explore the mechanism of Yigong San Prescription in treating bronchial asthma(BA)by using network pharmacology,molecular docking.Methods:The potential active constituents and corresponding targets of each Chinese medicinal of Yigong Powder were obtained through BATMAN-TCM,ETCM,SymMap,TCM Database@Taiwan and Traditional Chinese Medicine Systems Pharmoncology(TCMSP).DisGeNET,TTD,GeneCards,PharmGkb,Online Mendelian Inheritance in Man(OMIM),NCBI,Human Phenotypic Ontology(HPO)and Drugbank database were used to collect targets of action of BA.The Bioinformatics&Evolutionary Genomics was used to screen the common targets of medicine and disease.GEO was used to download gene chips,and R language was used to analyze and obtain differentially-expressed genes.Key targets were obtained through cross-validation with common target genes of medicine and disease,and an"active constituents-key targets"network was constructed.R software was used for gene ontology(GO)biological function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for key targets.The interaction relationship of key target proteins was obtained by using STRING database and Cytoscape software to screen out the core targets.AutoDock software was used to verify the molecular docking between the core targets and the active constituents.Results:A total of 176 active constituents and their corresponding 265 targets of action were screened,and 1263 differential genes were obtained.A total of 16 key targets including Pim-1 protooncogene(PIM1),β2 adrenergic receptor(ADRβ2),Recombinant V-Rel Reticuloendotheliosis Viral Oncogene Homolog A(RELA),carbonic anhydrase 2(CA2)gene and tumor necrosis factor(TNF)were identified by cross-validation.The associated active constituents were quercetin,glycyrrhizin A,glycyrrhizin B,kaempferol,naringin,etc..The key target enrichment pathways of Yigong San Prescription for BA included NOD-like receptor signaling pathway,C-type lectin receptor signaling pathway,TNF signaling pathway,etc..M

关 键 词：支气管哮喘 异功散 网络药理学 分子对接 

分 类 号：R562.2*5[医药卫生—呼吸系统]