Molecular mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis

Wang Qian; Shi Lei; Su Xuan; Zhang Ning; Ning Jie

doi:10.13406/j.cnki.cyxb.003812

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Molecular mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis

Basic research | 更新时间：2026-04-15

- Molecular mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis
- Journal of Chongqing Medical University Vol. 51, Issue 4, Pages: 547-553(2026)
- 作者机构：
  
  1.河北医科大学公共卫生学院实验中心，石家庄 050000
  2.河北医科大学公共卫生学院劳动卫生教研室，石家庄 050000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003812
  CLC： R563
- Received：11 October 2024，
  
  Revised：2025-02-06，
  
  Accepted：13 February 2025，
  
  Published：28 April 2026
- 稿件说明：
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王茜,石磊,苏旋等.SIRT1/NRF2信号通路调控肺驻留巨噬细胞参与肺纤维化的分子机制研究[J].重庆医科大学学报,2026,51(04):547-553.

Wang Qian,Shi Lei,Su Xuan,et al.Molecular mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis[J].Journal of Chongqing Medical University,2026,51(04):547-553.
王茜,石磊,苏旋等.SIRT1/NRF2信号通路调控肺驻留巨噬细胞参与肺纤维化的分子机制研究[J].重庆医科大学学报,2026,51(04):547-553. DOI： 10.13406/j.cnki.cyxb.003812.

Wang Qian,Shi Lei,Su Xuan,et al.Molecular mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis[J].Journal of Chongqing Medical University,2026,51(04):547-553. DOI： 10.13406/j.cnki.cyxb.003812.

摘要

目的

探究SIRT1/NRF2信号通路调控肺驻留巨噬细胞参与肺纤维化（pulmonary fibrosis，PF）损伤的可能机制。

方法

将30只小鼠分为对照组、PF组与PF+激活SIRT1组，每组10只。培养小鼠肺泡巨噬细胞（murine alveolar macrophage cell Line MH-S，MH-S）分为对照组、博来霉素组与博来霉素+激活SIRT1组。H&E染色检测肺组织病理变化。Masson染色检测小鼠肺组织纤维化水平。免疫荧光染色检测肺组织SIRT1、NRF2、TGF-β1与F4/80共表达情况。Western blot检测肺组织与巨噬细胞中SIRT1、NRF2及F4/80蛋白水平。RT-qPCR检测肺组织与巨噬细胞中SIRT1、NRF2 mRNA水平。ELISA试剂盒检测巨噬细胞TNF-α、IL-6及TGF-β1含量。

结果

与对照组相比，PF组小鼠肺泡间隔增厚，肺泡内具有大量分泌物及炎性细胞，肺间质可见大量纤维增生，小鼠肺组织SIRT1、NRF2蛋白及mRNA

水平减少（

0.05）；与PF组相比，PF+激活SIRT1组小鼠肺泡间隔厚度减少，肺泡内内分泌物及炎性细胞减少，肺泡间隔纤维增生减少，小鼠肺组织SIRT1、NRF2蛋白及mRNA水平增加（

0.05）。免疫荧光染色检测结果显示，PF小鼠肺组织中SIRT1、NRF2及纤维化标志蛋白TGF-β1分别与巨噬细胞标志蛋白F4/80存在共表达。与对照组相比，博来霉素组巨噬细胞SIRT1、NRF2蛋白及mRNA水平减少（

0.05），巨噬细胞活化相关标志蛋白F4/80蛋白水平增加，炎性因子TNF-α、IL-6含量及促纤维化因子TGF-β1含量增加（

0.05）；与博来霉素组相比，博来霉素+激活SIRT1组小鼠肺组织SIRT1、NRF2蛋白及mRNA水平增加（

0.05），F4/80蛋白水平减少，炎性因子TNF-α、IL-6含量及促纤维化因子TGF-β1含量减少（

0.05）。

结论

上调SIRT1/NRF2信号通路可抑制肺驻留巨噬细胞的活化及功能改善PF损伤。

Abstract

Objective

To investigate the possible mechanism of the SIRT1/NRF2 signaling pathway regulating lung-resident macrophages in pulmonary fibrosis（PF）.

Methods

A total of 30 mice were divided into control group，PF group，and PF+activated SIRT1 group，with 10 mice in each group. Mouse alveolar macrophages（MH-S） were divided into control group，bleomycin group，and bleomycin+activated SIRT1 group. HE staining was used to observe the pathological changes of lung tissue，and Masson staining was used to observe the level of lung fibrosis in mice. Immunofluorescent staining was used to measure the co-expression of SIRT1，NRF2，TGF-β1，and F4/80 in lung tissue. Western blotting was used to measure the protein expression levels of SIRT1，NRF2，and F4/80 in lung tissue and macrophages，and RT-qPCR was used to measure the mRNA expression levels of SIRT1 and NRF2 in lung tissue and macrophages. ELISA kits were used to measure the content of tumor necrosis factor-α（TNF-α），interleukin-6（IL-6），and transforming growth factor-β1（TGF-β1） in macrophages.

Results

Compared with the control group，the PF group had thickening of the alveolar septa，a large amount of secretions and inflammatory cells in the alveoli，a high degree of fibrosis in lung interstitium，and significant reductions in the protein and mRNA expres

sion levels of SIRT1 and NRF2 in lung tissue（

0.05）；compared with the PF group，the PF+activated SIRT1 group had significant reductions in the thickness of alveolar septa，the amount of secretions and inflammatory cells in alveoli，the degree of fibrosis in alveolar septa，and the protein and mRNA expression levels of SIRT1 and NRF2 in lung tissue（

0.05）. Immunofluorescent staining showed that SIRT1，NRF2，and the fibrosis marker protein TGF-β1 were co-expressed with the macrophage marker protein F4/80 in lung tissue of PF mice. Compared with the control group，the bleomycin group had significant reductions in the protein and mRNA expression levels of SIRT1 and NRF2 in macrophages（

0.05），as well as significant increases in the protein expression level of the macrophage activation-related marker protein F4/80 and the content of the inflammatory factors TNF-α and IL-6 and the pro-fibrotic factor TGF-β1（

0.05）； compared with the bleomycin group，the bleomycin+activated SIRT1 group had significant increases in the protein and mRNA expression levels of SIRT1 and NRF2 in lung tissue（

0.05），as well as significant reductions in the protein expression level of F4/80 and the content of the inflammatory factors TNF-α and IL-6 and the pro-fibrotic factor TGF-β1（

0.05）.

Conclusion

Upregulation of the SIRT1/NRF2 signaling pathway can inhibit the activation and function of lung-resident macrophages，thereby improving PF injury.

关键词

Keywords

references

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