中国病理生理杂志2025，Vol.41Issue(9)：1703-1712,10.DOI:10.3969/j.issn.1000-4718.2025.09.005
高海拔暴露驱动小鼠肺部血管功能、细胞外基质、凋亡与增殖相关基因表达改变并诱导肺损伤
High-altitude exposure induces lung injury in mice by altering expres-sion of genes associated with vascular function,extracellular matrix,apoptosis,and proliferation
摘要
Abstract
AIM:To investigate the types and mechanisms of lung injury induced by high-altitude exposure in mice.METHODS:Eight-week-old male C57BL/6 mice were randomly assigned to a normoxia group and a hypobaric hy-poxia exposure group,with 10 mice in each group.The hypobaric hypoxia group was continuously exposed to a hypobaric hypoxia environment simulating an altitude of 6 000 m for 3 d to establish an acute lung injury model.Lung tissues were collected.Lung pathological changes were evaluated using HE and Masson staining.Transcriptome analysis was conducted using DESeq2 and ClusterProfiler to identify differentially expressed genes and pathways,and hub genes were screened us-ing the STRING database.RESULTS:Compared with the normoxia group,the hypobaric hypoxia group exhibited signifi-cant increases in alveolar septal thickness,hyaline membrane formation,and neutrophil infiltration both in the alveolar space and the interstitial space,along with elevated lung injury scores(P<0.01),with no significant fibrosis observed.The mRNA levels of Alas2,Slc4a1,Rhag,Car1,Car2,Hbb,Agtr1b,Bmp2,Bmper,Vegfc,Foxm1,Fgf18,Igf1,Cx-cl12 and Mmp14 genes were significantly elevated(P<0.01),while Notch1,Notch4 and Cxcr4 mRNA levels were signifi-cantly decreased(P<0.01).Protein levels of inducible nitric oxide synthase(iNOS),cleaved caspase-3,cleaved PARP,fibronectin,elastin,tenascin C,tissue inhibitor of metalloproteinase-1(TIMP1),WNT3a,and β-catenin were signifi-cantly increased(P<0.05).CONCLUSION:Short-term high-altitude hypobaric hypoxia exposure induced acute lung in-jury in mice by significantly altering the expression of genes involved in apoptosis,vascular permeability regulation,extra-cellular matrix remodeling,and type Ⅱ alveolar epithelial cell proliferation.关键词
高海拔/肺损伤/转录物组/Ⅱ型肺泡上皮细胞Key words
high altitude/lung injury/transcriptome/type Ⅱ alveolar epithelial cells分类
医药卫生引用本文复制引用
张星宇,乐士冠,李轶,石祥广,王久存..高海拔暴露驱动小鼠肺部血管功能、细胞外基质、凋亡与增殖相关基因表达改变并诱导肺损伤[J].中国病理生理杂志,2025,41(9):1703-1712,10.基金项目
国家自然科学基金资助项目(No.U23A20475 （）
No.32200536) （）
科技部国家重点研发计划"发育编程及其代谢调节"重点专项项目(No.2023YFA1801200) （No.2023YFA1801200）
