基于网络药理学联合GEO芯片分析干姜黄芩黄连人参汤治疗2型糖尿病的机理和分子靶点  

Analysis of mechanism and molecular targets of Ganjiang Huangqin Huanglian Renshen formula in the treatment of type 2 diabetes based on network pharmacology and GEO chip

作　　者：张泽鑫 吴汶丰 谢丹 方舒涵 徐笋晶[2] ZHANG Zexin;WU Wenfeng;XIE Dan;FANG Shuhan;XU Sunjing(The Second Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510405 [2]广州中医药大学第一附属医院伤寒教研室,广东广州510405

出　　处：《广东药科大学学报》2020年第3期361-368,共8页Journal of Guangdong Pharmaceutical University

基　　金：广州市科技计划项目(201804010277)。

摘　　要：目的基于网络药理学联合GEO芯片差异基因分析的方法,分析干姜黄芩黄连人参汤治疗2型糖尿病的机理和分子靶点。方法在TCMSP和Drugbank数据库检索相关药物信息,限定物种为“Homo sapiens”,获得干姜黄芩黄连人参汤的活性成分和分子靶点。在GEO数据库检索疾病“Type 2 diabetes”,通过分析与筛选,获取GSE29221芯片数据,使用R软件获取其差异基因,绘制热图和火山图。通过cytoscape3.7.2构建干姜黄芩黄连人参汤与2型糖尿病差异基因分子靶点图,使用Bisogenet和CytoNCA绘制核心靶点拓扑网络,并进行药物与疾病基因的GO(BP、CC、MF)和KEGG分析。结果获得干姜黄芩黄连人参汤治疗2型糖尿病的49个活性成分,其治疗2型糖尿病的主要成分为槲皮素(quercetin)、黄芩素(wogonin)、山奈酚(kaempferol),以及与GEO共有差异基因55个,将差异基因进行PPI拓扑网络构建,筛选出候选基因8个,与KEGG通路富集基因合并,得到治疗2型糖尿病主要的9个基因为ERBB2、AKT1、EGF、PARP1、CDK2、EIF6、AHSA1、CAV1、HSPB1。GO生物过程731条,细胞成分31个,分子功能48个,主要涉及response to steroid hormone生物过程、cyclin-dependent protein kinase holoenzyme complex细胞成分,steroid hormone receptor activity分子功能等。KEGG通路11条,主要涉及HIF-1信号通路等。结论研究提供了干姜黄芩黄连人参汤在治疗2型糖尿病重要的分子靶标和机理,为其临床与实验应用提供基础。Objective To analyze the mechanism and molecular targets of Ganjiang Huangqin Huanglian Renshen formula(GHHRF)in the treatment of type 2 diabetes based on network pharmacology combined with GEO chip differential gene analysis.Methods Relevant drug information was retrieved from the TCMSP and Drugbank databases,and the restricted species was"Homo sapiens".The active ingredients and molecular targets of GHHRF were obtained.The disease"type 2 diabetes"was searched in the GEO database,and the GSE29221 chip data was obtained through analysis and screening.The differential software was used to obtain the differential genes and the heat map and volcano map were drawn.The molecular target maps of the differential gene of GHHRF and type 2 diabetes were constructed by cytoscape 3.7.2.The core target topology network was drawn using Bisogenet and CytoNCA.The GO(BP,CC,MF)and KEGG analysis of drug and disease genes were performed.Results 49 active ingredients of GHHRF for type 2 diabetes were obtained.The main components for treatment of type 2 diabetes were quercetin,wogonin and kaempferol.There were 55 differential genes shared with GEO and 8 candidate genes for PPI topology network.The main genes for type 2 diabetes included ERGG2,AKT1,EGF,PARP1,CDK2,EIF6,AHSA1,CAV1 and HSPB1.There were 731 GO biological processes,31 cell components and 48 molecular functions,mainly involving response to steroid hormone biological processes,cyclin dependent protein kinase holoenzyme complex cell components,and steroid hormone receptor activity molecular functions.There were 11 KEGG pathways,mainly involving HIF-1 signal pathway.Conclusion This study provides the important molecular target and mechanism of GHHRF in the treatment of type 2 diabetes,and provides the basis for its clinical and experimental application.

关 键 词：网络药理学 GEO芯片 干姜黄芩黄连人参汤 2型糖尿病 

分 类 号：R285.5[医药卫生—中药学]