中国实验动物学报2026，Vol.34Issue(4)：531-543,13.DOI:10.3969/j.issn.1005-4847.2026.04.006
基于代谢组学探究肺纤维化小鼠肺组织中潜在生物标志物及机制
Metabolomics-based exploration of potential biomarkers and mechanisms in lung tissue of mice with pulmonary fibrosis
摘要
Abstract
Objective Based on metabolomics technology,to clarify the specific endogenous biomarkers and their mechanisms in lung tissues of mice with pulmonary fibrosis.Methods Sixteen C57BL/6J mice were randomly divided into control group and bleomycin model(BLM)group.A mouse model of pulmonary fibrosis was established.Indicators such as lung function,lung pathology,and hydroxyproline(HYP)levels were detected in each group.Correlation analysis and value evaluation between key differential metabolites and pathological indicators were performed to screen potential biomarkers,followed by functional analysis and pathway enrichment.A multi-layered"biomarker-disease-related target-pathway"interaction network was constructed to clarify the core mechanisms of biomarkers in pulmonary fibrosis.Additionally,qPCR was used to detect the mRNA levels of core targets.Results Compared with the control group,mice in the BLM group showed significant reductions in body mass and lung function(P＜0.01),accompanied by disordered lung tissue structure,damaged alveolar walls,and increased lung coefficient and lung tissue collagen levels(HYP)(P＜0.01).Metabolomics result revealed altered metabolic profiles in mice with pulmonary fibrosis,with differential metabolites primarily enriched in the arachidonic acid metabolism pathway.Correlation analysis and value evaluation of the top 10 significant differential metabolites identified 8 biomarkers significantly associated with pulmonary fibrosis characteristics(P＜0.01,P＜0.01,P＜0.05).The multi-layered interaction network indicated that the core mechanisms of these biomarkers mainly involve inflammatory responses and cell proliferation.qPCR result showed that 6 core targets were significantly upregulated in lung tissues of mice with pulmonary fibrosis(P＜0.05,P＜0.01).Conclusions The metabolic profile of mice with pulmonary fibrosis is altered.Biomarkers such as Capryloylglycine,S-(PGA1)-glutathione,Corticosterone,Thymidine,3-Oxotetradecanoic acid,3-Hydroxybutyric acid,Uridine,and 3-Hydroxysebacic acid may play important roles in the progression of IPF by regulating inflammatory responses and cell proliferation through targets including IL-6,EGFR,CXCL8,MMP9,PTGS2,and MAPK3.关键词
博来霉素/肺纤维化/代谢组学/差异代谢物Key words
bleomycin/pulmonary fibrosis/metabolomics/differential metabolite分类
生物科学引用本文复制引用
谢云云,杨帆,孙淑仃,彭云鹏,孙鑫,卢瑞龙,田燕歌..基于代谢组学探究肺纤维化小鼠肺组织中潜在生物标志物及机制[J].中国实验动物学报,2026,34(4):531-543,13.基金项目
河南省科技研发计划联合基金(优势学科培育类)重点项目(232301420020),国家区域联合基金重点项目(U23A20503),四大慢病重大专项(2024ZD0522905).Funded by Henan Province Science and Technology Research and Development Plan Joint Fund(Advantageous Discipline Cultivation Category)Key Project(232301420020),Regional Innovation and Development Joint Funds of the National Natural Science Foundation of China(U23A20503),Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0522905). （优势学科培育类）
