中国实验动物学报2025，Vol.33Issue(6)：848-857,10.DOI:10.3969/j.issn.1005-4847.2025.06.007
LPS诱导的小鼠急性肺损伤后肺纤维化模型构建与机制研究
Construction and mechanism of pulmonary fibrosis model in mice induced by lipopolysaccharide-induced acute lung injury
摘要
Abstract
Objective The progression of pulmonary fibrosis is a common clinical issue after acute lung injury(ALI).We aimed to construct a model simulating clinical ALI-induced pulmonary fibrosis by repeated challenges with lipopolysaccharide(LPS).We then observed the development from ALI to pulmonary fibrosis,to explore the possible mechanisms mediating the transition from inflammatory injury to fibrosis.Methods Mice were treated with LPS(1,2,4,8 mg/kg)intranasally to induce ALI.At 7 d,14 d,21 d,28 d,35 d,and 42 d after modeling respectively,α-smooth muscle actin(SMA),collagen 1(Col-1),and hydroxyproline levels in lung tissue,and collagen fiber deposition were observed by Masson staining and compared to determine the process and degree of fibrosis formation in different modeling method.Expression changes in interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and transforming growth factor(TGF)-β1 in lung tissue at each time point were detected to explore the mechanisms of fibrosis formation.Results Treatment of mice with 1,4,and 4 mg/kg LPS for 3 consecutive days(M-1 group)result ed in a stable ALI-induced pulmonary fibrosis model.Masson staining showed that α-SMA,Col-1,hydroxyproline,and collagen fiber deposition in the lung tissue began to increase in M-1 group mice in a time-dependent manner after 7 d.Collagen deposition in the lung tissue interstitium was significantly increased at 21 d post-modeling,and fibrosis indicators were significantly increased at 28 d,compared with control mice.Collagen deposition continued to increase until 42 d.Hydroxyproline and collagen fibers in the lung tissue in the other model groups with different doses and hit times did not increase significantly compared with the control group.TGF-β1 expression detected by Western blot began to increase gradually 14 d after modelling in the M-1 group,and was significantly higher than in the control group at 28 d.The pro-inflammatory cytokines TNF-α and IL-1β increased significantly on day 7(acute phase),and TNF-α expression continued to increase until 28 d,while IL-1β gradually decreased after day 7.TNF-α and IL-1β in the lung tissue both continued to decrease after the acute phase in the other model groups without fibrosis.Conclusions LPS 1,4,and 4 mg/kg for 3 consecutive days can be used to construct an ALI/acute respiratory distress syndrome-induced pulmonary fibrosis model,via a mechanism that may be related to the sustained high expression of TNF-α regulating TGF-β1 to induce fibroblast activation and proliferation.关键词
急性肺损伤/肺纤维化/脂多糖/炎症/模型Key words
acute lung injury/pulmonary fibrosis/lipopolysaccharide/inflammation/model分类
生物科学引用本文复制引用
梁晓,李昂昂,彭勍,刘建勋,李军梅..LPS诱导的小鼠急性肺损伤后肺纤维化模型构建与机制研究[J].中国实验动物学报,2025,33(6):848-857,10.基金项目
中国中医科学院科技创新工程(CI2021A04603).Funded by China Academy of Chinese Medical Sciences Science and Technology Innovation Project(CI2021A04603). （CI2021A04603）
