五虎汤干预咳嗽变异性哮喘自噬的生物信息学研究  

Bioinformatics study on Wu Hu Tang interfering with autophagy in cough variant asthma

作　　者：胡燕[1] 王孟清[1] 李玲 姚冰 邓羿駃 HU Yan;WANG Mengqing;LI Ling;YAO Bing;DENG Yixin(Department of Pediatrics,the First Hospital of Hunan University of Chinese,Changsha 410007,China;College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410036,China)

机构地区：[1]湖南中医药大学第一附属医院儿科,长沙410007 [2]湖南中医药大学中医学院,长沙410036

出　　处：《中国免疫学杂志》2024年第11期2322-2329,共8页Chinese Journal of Immunology

基　　金：湖南省教育厅科学研究项目(20B440);湖南省自然科学基金项目(2021JJ40422);湖南省中医药管理局重点课题(A2024027);全国名老中医药专家传承工作室(国中医药人教函[2022]75号)。

摘　　要：目的:五虎汤具有治疗咳嗽变异性哮喘(CVA)的作用,但其具体作用机理仍需进一步探究或阐明。方法:从中药系统药理学数据库与分析平台(TCMSP)、中药分子机制的生物信息学分析工具(BATMAN-TCM)及中医药整合药理学研究平台v2.0(TCMIP)、PubChem、Chemspider、Swiss Target Prediction、GEO、GeneCards等数据库中获取和挖掘五虎汤的活性成分、预测靶点、自噬基因、CVA基因及哮喘的差异表达基因(DEGs),利用线韦恩图交集工具取交集获取关键基因,使用Cytoscape3.8.0软件构建活性成分-关键网络;五虎汤干预CVA自噬靶点与自噬基因的相关性分析;使用STRING数据库、Cytohubba插件构建蛋白互作网络及核心基因筛选。运用R语言Biomanager、ClusterProfiler包进行关键靶点GO、KEGG富集分析,最后进行分子对接。结果:收集并筛选出五虎汤活性成分42个,潜在作用靶点536个,自噬相关基因7 236个,CVA基因1 987个,DEGs 460个,取交集后共获得13个关键靶点,运用Wilcoxon非参数检验验证,发现12个基因差异具有统计学意义。富集分析结果显示,这些靶基因主要通过VEGF信号通路、部分氨基酸代谢通路在细胞自噬中发挥作用。结论:五虎汤通过多成分、多层次、多靶点参与自噬相关过程达到干预CVA的目的,促进了中西医结合治疗CVA思路的发展,为临床新药研发提供了新视角。Objective:Although Wu Hu Tang has the effect of treating cough variant asthma(CVA),its specific mechanism of action remains unclear.Methods:Predicted targets,autophagy genes,cough variant asthma genes and differentially expressed genes(DEGs)of CVA of Wu Hu Tang were obtained and mined from the Traditional Chinese Medicine Systematic Pharmacology Data-base and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BAT-MAN-TCM)and TCM Integrated Pharmacology Research Platform v2.0(TCMIP),PubChem,Chemspider,Swiss Target Prediction,GEO,GeneCards and other databases.The intersection tool of line Venn diagram was used to obtain the key genes.Using Cyto-scape3.8.0 software build active ingredient-key network;Wu Hu Tang intervention CVA autophagy targets with autophagy genes corre-lation analysis;Use the STRING database,Cytohubba plug-in build protein interaction network and core gene screening.GO and KEGG enrichment analysis of key targets were performed using R Biomanager and ClusterProfiler package,and finally molecular dock-ing was performed.Results:A total of 42 active ingredients,536 potential action targets,7236 autophagy-related genes,1987 CVA genes and 460 DEGs of Wu Hu Tang Tang were collected and screened.Thirteen key targets were obtained after taking the intersec-tion,and 12 genes were found to be statistically significant by validated used wilcoxon non-parametric test.The results of the enrich-ment analysis showed that these target genes mainly functioned in cellular autophagy through the VEGF signaling pathway,and some amino acid metabolic pathways.Conclusion:Wu Hu Tang is capable of multi-component,multi-level and multi-target involvement in autophagy-related processes to achieve intervention in CVA,which promotes the development of the idea of combining Chinese and Western medicine in the treatment of CVA and provides a new idea for the development of new clinical drugs.

关 键 词：咳嗽变异性哮喘 五虎汤 自噬 生物信息学 分子对接 

分 类 号：R272[医药卫生—中医儿科学]