中国病理生理杂志2024，Vol.40Issue(12)：2393-2400,8.DOI:10.3969/j.issn.1000-4718.2024.12.026
博来霉素多次给药诱导小鼠肺纤维化模型的建立及评价
Establishment and evaluation of a model of pulmonary fibrosis induced by multiple administration of bleomycin in mice
摘要
Abstract
AIM:To establish a mouse model of pulmonary fibrosis induced by multiple intratracheal instilla-tions of bleomycin(BLM).METHODS:C57BL/6J mice were randomly divided into five groups:control group(n=5),multiple high-dose BLM(BLM-MH)group(n=10),multiple medium-dose BLM(BLM-MM)group(n=8),multiple low-dose BLM(BLM-ML)group(n=7),and single medium-dose BLM(BLM-SM)group(n=6).The pulmonary fibrosis mod-el was induced by single or multiple intratracheal instillations of BLM.Survival curves were plotted at day 56,and lung tis-sue was collected for lung coefficient calculation.Pathological changes in lung tissue were assessed using hematoxylin-eo-sin(H&E)staining and Masson staining.Indicators of lung fibrosis,such as hydroxyproline(HYP),were measured.Dif-ferentially expressed genes in patients with IPF were screened using the GEO database,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed to identify pathways associated with IPF.Western blot was used to detect changes in these pathways in the lung tissues of the model mice.RESULTS:The survival rates were 50%in the BLM-MH group and 87.5%in the BLM-MM group,with no deaths in other groups.Compared with the control group,the BLM-MH and BLM-MM groups showed significantly increased lung coefficients(P＜0.05),lung tissue dam-age,inflammation levels,degree of pulmonary fibrosis(P＜0.05 or P＜0.01),and HYP content.The BLM-MH and BLM-MM groups,compared with the BLM-SM group,showed significantly elevated levels of inflammation,fibrosis,and HYP content(P＜0.05 or P＜0.01).GEO database and KEGG enrichment analysis revealed that the extracellular matrix-recep-tor interaction pathway(ECM-RIP)may be involved in IPF development.The expression levels of ECM-RIP pathway-re-lated proteins,such as phosphorylated focal adhesion kinase(p-FAK)and phosphorylated Src protein(p-Src),were in-creased in the lung tissues of the model mice compared with the control group.Compared with the BLM-SM group,the BLM-MH group exhibited significant increases in the protein levels of p-FAK and p-Src in the lung tissue(P＜0.05).CONCLUSION:The murine model of pulmonary fibrosis established through repeated intratracheal instillations of BLM effectively mimics the pathological characteristics of the disease,providing a valuable experimental model for the investiga-tion of idiopathic pulmonary fibrosis pathogenesis and for the development of therapeutic agents.关键词
肺纤维化/博来霉素/动物模型/模型评价Key words
pulmonary fibrosis/bleomycin/animal model/model evaluation分类
医药卫生引用本文复制引用
桑星洁,张琴,关庆洲,赵鹏,邢小香,白云苹..博来霉素多次给药诱导小鼠肺纤维化模型的建立及评价[J].中国病理生理杂志,2024,40(12):2393-2400,8.基金项目
国家自然科学基金项目(No.81904170 （）
No.U23A20503) （）
