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Updated: Aug 6, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
[Kinetics and mechanism in bleomycin-induced murine pulmonary fibrosis model]
1Department of Respiratory Medicine, People's Hospital, Peking University, Beijing 100044, China. huping_wind@yahoo.com.cn
Objective:
To investigate the kinetics of pathogenesis of bleomycin induced pulmonary fibrosis and its mechanism in mice.
Methods:
Thirty six male ICR mice were randomized as a negative control (NC) group and pulmonary fibrosis model (FM) groups (FMA, FMB, FMC, FMD, FME sub groups). Except for NC group, mice in the other groups were given bleomycin by nasal instillation. Animals in each group were sacrificed on day 6, 14, 21, 28 and 35, respectively. T lymphocytes were quantified for Th1/Th2 and Tc1/Tc2 by flow cytometry. Accumulation of inflammatory cells in bronchioalveolar lavage fluid (BALF) was quantified by cell count. The sections of the right lung were stained with either hematoxylin eosin (HE) or Masson trichrome. The left lung was weighed and its hydroxyproline (HYP) content was assayed. Multi cytokine expression in lung tissue was assayed by semi quantitative reverse transcription polymerase chain reaction (RT-PCR). On day 35, the tidal volume (V(T)), forced expiratory volume in 1 second/forced vital capacity (FEV 0.1/FVC), static compliance (Cst) of mice were determined before they were sacrificed.
Results:
(1)The total cell number in BALF in pulmonary fibrosis groups was statistically significantly higher than that in NC group (all P<0.01), and HYP content in lung tissue in pulmonary fibrosis groups was statistically significantly increased than that in NC group except for group FMA (all P<0.01). (2)V(T) and Cst in FME group were statistically significantly decreased than those in NC group (both P<0.01), and FEV 0.1/FVC was statistically significantly increased (P<0.05). (3)Th1 and Tc1 were demonstrated as the dominant expression in the acute inflammatory stage; Th2 and Tc2 were the dominant expression in the fibrosis forming stage, and then Th1 and Tc1 were again the dominant expression at the terminal stage of pulmonary fibrosis. (4)Compared with the content of cytokine in the lung in NC group, the expression of transforming growth factor-beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA were significantly higher in FM groups (all P<0.01).
Conclusion:
The changes in lung function of bleomycin-induced pulmonary fibrosis in mice are typical of that of restrictive ventilatory disorder. Th2, Tc2 and fibrotic promoting growth factors (TGF-beta1, TIMP-1, etc.) play pivotal roles in the pathogenesis of pulmonary fibrotic process.
Insights
Bleomycin-induced pulmonary fibrosis in mice shows typical restrictive lung function changes. T-helper 2 (Th2) cells, cytotoxic T-2 (Tc2) cells, and fibrotic factors like TGF-beta1 are key to this lung disease progression.
Area of Science:
- Pulmonary Medicine
- Immunology
- Pathogenesis Research
Context:
- Bleomycin is a chemotherapeutic agent known to induce pulmonary fibrosis.
- Understanding the temporal dynamics and cellular mechanisms of bleomycin-induced pulmonary fibrosis is crucial for developing targeted therapies.
Purpose:
- To investigate the kinetics of pathogenesis in bleomycin-induced pulmonary fibrosis.
- To elucidate the underlying immunological and molecular mechanisms in a mouse model.
Summary:
- Mice treated with bleomycin exhibited increased inflammatory cells in bronchoalveolar lavage fluid and elevated hydroxyproline content in lung tissue.
- Lung function tests revealed restrictive ventilatory disorder characteristics.
- Flow cytometry demonstrated a shift in T-lymphocyte populations (Th1/Tc1 to Th2/Tc2 and back) correlating with disease stages.
- Gene expression analysis showed increased levels of TGF-beta1 and TIMP-1 mRNA.
Impact:
- This study highlights the dynamic role of T-lymphocyte subsets and fibrotic growth factors in the pathogenesis of pulmonary fibrosis.
- Findings provide insights into the progression of bleomycin-induced lung injury, aiding in the development of potential therapeutic strategies.
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