基于GEO芯片与网络药理学初探板蓝根治疗儿童鼻病毒感染的作用机制  

Mechanism of Action of Isatidis Radix in the Treatment of Children with Rhinovirus Infection:A Preliminary Study Based on GEO Chip and Network Pharmacology

作　　者：张卫娜 刘明 郑丽[1] 孙雪林[3] ZHANG Wei-na;LIU Ming;ZHENG Li;SUN Xue-lin(Department of Pharmacy,AMHT Group Aerospace 731 Hospital,Beijing 100074,China;School of Basic Medical Sciences of Lanzhou University,Lanzhou 730000,China;Department of Pharmacy,Beijing Hospital,Beijing 100010,China)

机构地区：[1]中国航天科工集团七三一医院药学部,北京100074 [2]兰州大学基础医学院,兰州730000 [3]北京医院药学部,北京100010

出　　处：《中国合理用药探索》2023年第7期56-67,共12页Chinese Journal of Rational Drug Use

基　　金：国家重点研发计划资助项目(2020YFC2009001)。

摘　　要：目的:利用网络药理学与生物信息学探索板蓝根治疗儿童鼻病毒感染的作用机制。方法:从中药系统药理学数据库与分析平台(TCMSP)、中国台湾中医药资料库、传统中药数据库及文献数据库中筛选板蓝根的有效化合物与作用靶点。从GEO数据库中筛选健康儿童与感染鼻病毒儿童的差异表达基因。对板蓝根作用靶点与疾病差异表达基因取交集,利用R4.2.0与Cytoscape 3.8.0软件构建靶基因PPI网络及拓扑分析、进行GO富集及KEGG信号通路富集分析。结果:板蓝根有23个有效化合物能与25个在感染鼻病毒儿童中差异表达的基因所对应靶蛋白结合发挥治疗作用。通过构建核心PPI网络发现靶基因BRKCA、MAPK14、JUN、CDKN1A、GSK3B和IKBKB在治疗中非常关键。GO富集分析发现靶基因可能参与的生物过程有腺体分泌、线粒体外膜通透性的正调控、DNA损伤致细胞凋亡信号通路的激活等;可能影响的细胞组份有蛋白激酶、细胞孔隙、周期蛋白依赖性蛋白激酶等;可影响G蛋白偶联神经递质受体的激活、G蛋白偶联胺受体的激活、DNA转录因子受体的激活等来改变分子功能。KEGG信号通路分析发现靶基因参与了多条病毒感染相关信号通路,如EB病毒感染、人类免疫缺陷病毒1型(HIV-1)感染、卡波西肉瘤相关疱疹病毒(KSHV)感染与人类巨细胞病毒(CMV)感染。结论:板蓝根可通过多成份、多靶点、参与多个生物过程及多条信号通路来治疗儿童鼻病毒感染,为药物开发提供了理论基础及新的参考依据。Objective:To explore the mechanism of action(MOA)of Isatidis Radix in the treatment of children with rhinovirus infection by means of network pharmacology and bioinformatics.Methods:The effective compounds and targets of Isatidis Radix were collected by screening the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Dadabase@ China Taiwan,the conventional TCM database and the literature databases.Differentially expressed genes between healthy children and children infected with rhinovirus were screened from the GEO database.The targets of Isatidis Radix and differentially expressed genes were intersected to construct the PPI network of target genes using R 4.2.0 and Cytoscape 3.8.0 software for topological analysis,GO enrichment analysis and KEGG pathway enrichment analysis.Results:Twenty-three effective compounds of Isatidis Radix could bind to the target proteins from 25 differentially expressed genes in children infected with rhinovirus.Critical target genes for treatment were identified during the construction of a core PPI network,including BRKCA,MAPK14,JUN,CDKN1A,GSK3B and IKBKB.GO enrichment analysis revealed that target genes were possibly involved in some biological processes,including gland development,positive regulation of mitochondrial outer membrane permeability,and activation of DNA damage-induced apoptosis signaling pathway.The analysis also revealed possibly affected cellular components,including protein kinase,cellular pore,cyclin-dependent protein kinase,etc.The target genes possibly affected the activation of G proteincoupled neurotransmitter receptors,G protein-coupled amine receptors,DNA transcription factor receptors,which further changed molecular functions.Analysis of the KEGG signaling pathway found that the target genes were involved in multiple signaling pathways related to viral infections,such as human herpes virus infection,human immunodeficiency virus type 1 infection,Kaposi sarcoma-associated herpesvirus infection

关 键 词：板蓝根 儿童 鼻病毒感染 网络药理学 生物信息学 作用机制 

分 类 号：R725.6[医药卫生—儿科]