世界中西医结合杂志2025，Vol.20Issue(10)：1925-1935,11.DOI:10.13935/j.cnki.sjzx.251003
基于衰老相关基因的慢性阻塞性肺疾病机制探讨及中药筛选
Mechanisms of Chronic Obstructive Pulmonary Disease and Screening of Chinese Medicine Based on Senescence-Associated Genes
摘要
Abstract
Objective To identify aging-related target genes associated with chronic obstructive pulmonary dis-ease(COPD)based on the Aging Atlas and Gene Expression Omnibus(GEO)databases,explore the molecular mechanisms of COPD-related aging,and screen potential Chinese medicines for intervention,thereby providing theoretical support for both basic and clinical research on COPD aging and for the precision-based syndrome differentiation and treatment in tra-ditional Chinese medicine(TCM).Methods Transcriptome data from GEO were used to screen differentially expressed genes(DEGs),which were then intersected with senescence-associated genes(SAGs)from the Aging Atlas database to obtain COPD aging-related target genes.Correlation analysis was performed using the correlation function(cor).Immune infiltration was analyzed using the Cell Identity by Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algo-rithm.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were conducted.The target gene-miRNA interactions were predicted through miRWalk,RNA22,RNAInter,and TargetScan databases,and their intersections were used to construct a regulatory network.Potential therapeutic Chinese medicines were screened via the Coremine Medical database.Results Fourteen key COPD aging-related target genes were identified,including five upregulated and nine downregulated genes.Among them,ζ-chain-associated protein kinase 70(ZAP70),CD40 ligand(CD40LG),interleukin-7 receptor(IL7R),baculoviral IAP repeat-containing protein 3(BIRC3),and B-cell lympho-ma 2(BCL2)were positively correlated with clinical pulmonary function indices,whereas interleukin-15(IL 15),aldehyde dehydrogenase 2(ALDH2),and transcriptional repressor GATA binding 1(TRPS1)showed negative correlations.Immune infiltration analysis revealed that monocytes and CD8+T cells exhibited the highest correlations with target genes.Enrich-ment analyses indicated that the nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway and apoptosis were major aging-related pathways,while biological process(BP)terms were significantly enriched in immune cell regulation.The identified Homo sapiens microRNAs(hsa-miR-103a-3p and hsa-miR-122-5p)showed potential regulatory relationships with target genes.Moreover,Chinese medicines such as Arnebiae Radix and Herba Hedyotidis Diffusae were found to be of great significance in COPD aging research.Conclusion The analysis of COPD ag-ing-related target genes contributes to a deeper understanding of COPD aging mechanisms,facilitates the discovery of new therapeutic targets and clinical applications,and provides novel insights for both the basic and clinical research of COPD aging as well as for the precision-based syndrome differentiation and treatment in TCM.关键词
慢性阻塞性肺疾病/衰老相关基因/生物信息学/免疫浸润/信号通路/miRNA/中药Key words
Chronic Obstructive Pulmonary Disease/Senescence-Associated Genes/Bioinformatics/Immunologi-cal Infiltration/Signaling Pathway/MiRNA/Chinese Medicine分类
医药卫生引用本文复制引用
黄迪,赵继亭,张雪玲,梁明昊,许一飞,阮梽珅,邱占军,陈宪海..基于衰老相关基因的慢性阻塞性肺疾病机制探讨及中药筛选[J].世界中西医结合杂志,2025,20(10):1925-1935,11.基金项目
国家自然科学基金面上项目(82374379) （82374379）
济南市临床医学科技创新计划(202134065) （202134065）
山东省中医药科技发展计划项目(2019-0967) （2019-0967）
