中国实验动物学报2025，Vol.33Issue(10)：1403-1411,9.DOI:10.3969/j.issn.1005-4847.2025.10.001
衰老与特发性肺纤维化的相关性及关联的分子机制
Molecular association between aging and idiopathic pulmonary fibrosis pathogenesis
摘要
Abstract
Objective To explore the correlation between aging and idiopathic pulmonary fibrosis(IPF)and reveal the underlying molecular mechanisms.Methods IPF models were established using young(2-month-old)and aged(18-month-old)C57BL/6J mice by intratracheal instillation of bleomycin(BLM)hydrochloride(2.5 mg/kg)after fully exposing the trachea.The control groups received an equal volume of saline administered in the same manner.Mice were divided randomly into four groups:a young control(Ctrl-Y)group,young model(IPF-Y)group,aged control(Ctrl-A)group,and aged model(IPF-A)group.Histopathological changes were evaluated by hematoxylin-eosin and Masson staining.Collagen type Ⅰ alpha 1 chain(COL1A1),α-smooth muscle actin(SMA),and fibronectin(FN)expression were detected by immunohistochemistry.Cell senescence was detected by senescence-associated beta-galactosidase(SA-β-Gal)staining.Differentially expressed genes were detected by transcrip tome sequencing,followed by gene ontology functional annotation(GO)and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Core gene expression was validated by quantitative reverse transcription-polymerase chain reaction.Results The fibrosis score was significantly higher in the IPF-A group compared with the IPF-Y group(P＜0.05).Expression levels of α-SMA,and FN were significantly upregulated in the IPF-A group versus the IPF-Y group by 36％,and 25％,respectively(P＜0.05).The SA-β-Gal-positive area indicating senescence was significantly larger in the IPF-A group than in the IPF-Y group.Fifty-five senescence-IPF interactive genes were identified,among which Cdkn1a,MMP3,and Pdcd1 were synergistically upregulated in the IPF-A group(P＜0.05).KEGG analysis revealed the activation of signaling pathways such as extracellular matrix(ECM)-receptor interaction,phagosome,cytokine-cytokine receptor interaction,efferocytosis,and PI3K-Akt(FDR＜0.05).Conclusions aging promotes IPF progression,which induces lung tissue senescence.The underlying mechanism may involve ECM remodeling driven by immunosenescence,inflammatory accumulation,and metabolic disorders.关键词
肺纤维化/IPF/衰老/转录组学Key words
pulmonary fibrosis/idiopathic pulmonary fibrosis/aging/transcriptomics分类
生物科学引用本文复制引用
李书晴,王艳芳,莫丽莎,刘良徛,柯诗文..衰老与特发性肺纤维化的相关性及关联的分子机制[J].中国实验动物学报,2025,33(10):1403-1411,9.基金项目
国家自然科学基金(82305162,82405334),江西省2024年研究生创新专项(YC2024-B218),江西省自然科学基金(20232BAB206145),中医肺科学江西省重点实验室(2024SSY06321),江西中医药大学校级科技创新团队发展计划(CXTD22011).Funded by the National Natural Science Foundation of China(82305162,82405334),the 2024 Graduate Innovation Special Project of Jiangxi Province(YC2024-B218),the Natural Science Foundation of Jiangxi Province(20232BAB206145),Jiangxi Province Key Laboratory of Traditional Chinese Medicine-Pulmonary Science(2024SSY06321),Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(CXTD22011). （82305162,82405334）
