摘要
目的:通过生物信息学方法探讨重症支气管哮喘[简称重症哮喘(SA)]的差异表达基因,分析其作用机制,并筛选潜在具有治疗作用的中药及活性成分。方法:在高通量基因表达(GEO)数据库中选取GSE136587和GSE158752数据集,利用R软件对数据集进行差异分析获得差异表达基因,并进行蛋白-蛋白相互作用(PPI)网络分析,筛选核心基因,寻找关键通路和枢纽基因。最后将核心基因提交至Coremine数据库筛选具有潜在治疗作用的中药,并通过《中华医典》检索相关中药方剂。结果:共筛选出466个差异表达基因。通过STRING平台构建PPI网络共筛选包括25 kDa突触关联蛋白(SNAP25)、谷氨酸离子型受体2(GRIA2)、轴突蛋白1(NRXN1)、钾电压门控通道亚家族A成员1(KCNA1)、突触囊泡蛋白1(SYT1)和嗜铬蛋白A(CHGA)等核心靶点25个。基因本体(GO)功能富集显示SA的生物学过程与细胞趋化性和白细胞迁移等有重要关系,京都基因与基因组百科全书(KEGG)富集的通路主要涉及骨髓白细胞迁移、白细胞趋化性、细胞趋化性、白细胞迁移、对外部刺激反应的正向调节和骨髓白细胞活化等信号通路。采用网络药理学方法基于核心靶点筛选得到具有潜在治疗SA作用的中药367种,其中人参、水牛角、全蝎和黄芪等中药涉及多个核心靶点,与SA具有高度相关性,在《中华医典》中检索具有高度相关性的中药,共得到17个潜在具有治疗效果的中药方剂。结论:通过生物信息学筛选SA的潜在标志物和具有治疗作用的中药,为SA早期诊断和发病机制研究提供新的靶点,为其治疗的中药方剂研发提供思路。
Objective:To discuss the differentially expressed genes in severe bronchial asthma[severe asthma(SA)]by bioinformatics methods and analyze their mechanisms,and to screen the traditional Chinese medicines and their active components with potential therapeutic effects.Methods:The GSE136587 and GSE158752 datasets were selected from the Gene Expression Omnibus(GEO)Database;R software was used for the differential analysis to obtain the differentially expressed gene;the protein-protein interaction(PPI)network analysis was used to screen the core genes,and the key pathways and hub genes were identified.The core genes were uploaded to the Coremine Database to screen for the traditional Chinese medicines with the potential therapeutic effects,and the relevant Chinese herbal prescriptions were searched in Chinese Medical Dictionary.Results:A total of 466 differentially expressed genes were screened.The PPI network constructed through the STRING platform led to the selection of synaptosomal associated protein 25 kDa(SNAP25),glutamate ionotropic receptor AMPA type subunit 2(GRIA2),neurexin 1(NRXN1),potassium voltage-gated channel subfamily a member 1(KCNA1),synaptotagmin 1(SYT1),and chromogranin A(CHGA).The Gene Ontology(GO)functional enrichment analysis results showed that the biological processes of SA were significantly related to the cellular chemotaxis and leukocyte migration.The Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways enrichment mainly involve bone marrow leukocyte migration,leukocyte chemotaxis,cell chemotaxis,leukocyte migaration,up-regulation of outside stimulus,and bone marrow leukocyte activation signaling pathways.Network pharmacology was applied to screen for 367 traditional Chinese medicines with potential therapeutic effects based on the core targets.Among them,ginseng,water buffalo horn,scorpio,and astragalus,which involve multiple core targets,were highly related to SA.A total of 17 potential Chinese herbal prescriptions with therapeutic effects were retrieved from Chinese Medical Dictionary.Conclusion:The bioinformatics screening of potential biomarkers and traditional Chinese medicines with therapeutic effects for SA provides the new targets for the early diagnosis and research on the pathogenesis of SA,and offers new insights into the development of herbal prescriptions for its treatment.
作者
陈丽平
韩立
卞华
庞立业
CHEN Liping;HAN Li;BIAN Hua;PANG Liye(Henan Provincal Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immuoregulation,Nanyang Institute of Technology,Nanyang 473004,China;Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of China,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China)
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2024年第2期411-421,共11页
Journal of Jilin University：Medicine Edition
基金
国家自然科学基金青年科学基金项目(81704200)
第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]239号)
河南省科技厅科技攻关项目(222102310551)
河南省科技厅自然科学基金项目(232300421192)。
关键词
重症哮喘
差异表达基因
生物信息学
中药筛选
Severe asthma
Differentially expressed gene
Bioinformatics
Screening of Chinese medicine
