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Updated: Jun 24, 2026
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
Salvinorin A Alleviates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting M2 Macrophage Polarization and
Li Xu1, Aijuan Sun2, Yanyan Liu1
1Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Introduction:
Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited treatment options. Macrophages, as the primary immune cells in the lungs, play a key role in the progression of pulmonary fibrosis. Salvinorin A (SA), a naturally occurring non-nitrogenous diterpenoid, exhibits anti-inflammatory and anti-neuropathic pain effects in various models. However, whether SA alleviates bleomycin-induced pulmonary fibrosis by modulating macrophage function remains unclear.
Methods:
This study aimed to investigate the therapeutic effects and mechanisms of SA on bleomycin-induced pulmonary fibrosis in mice. A bleomycin-induced pulmonary fibrosis mouse model was established, and SA was administered via intraperitoneal injection starting from day 7 post-modeling. The study further explored the effects of SA on M2 macrophage polarization and macrophage-to-myofibroblast transition (MMT) both in vivo and in vitro.
Results:
SA treatment significantly alleviated the degree of pulmonary fibrosis and inflammatory response, improved lung tissue pathological structure, and reduced extracellular matrix deposition and the release of related inflammatory cytokines. Mechanistic studies revealed that SA effectively inhibited M2 macrophage polarization both in vivo and in vitro, as evidenced by the downregulation of marker molecules such as CD206, Arg1, Fizz1, and YM1. Additionally, SA also inhibited MMT, specifically manifested as a significant decrease in the proportion of α-SMA⁺CD68⁺ double-positive cells.
Conclusion:
This study reveals that SA can effectively alleviate the progression of pulmonary fibrosis by dually inhibiting M2 macrophage polarization and the MMT process, providing important experimental evidence for SA as a potential therapeutic agent against pulmonary fibrosis.
Insights
Salvinorin A (SA) effectively treats pulmonary fibrosis by inhibiting M2 macrophage polarization and macrophage-to-myofibroblast transition (MMT). This study provides evidence for SA as a potential therapeutic for this progressive lung disease.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Pulmonary fibrosis (PF) is a fatal lung disease with few treatments.
- Macrophages are key immune cells driving PF progression.
- Salvinorin A (SA) has anti-inflammatory properties, but its effect on PF is unknown.
Purpose of the Study:
- Investigate SA's therapeutic effects on bleomycin-induced PF in mice.
- Elucidate SA's mechanism involving macrophage function and MMT.
Main Methods:
- Established a bleomycin-induced PF mouse model.
- Administered SA via intraperitoneal injection.
- Assessed SA's impact on M2 macrophage polarization and MMT in vivo and in vitro.
Main Results:
- SA treatment reduced PF severity, inflammation, and extracellular matrix deposition.
- SA inhibited M2 macrophage polarization (downregulating CD206, Arg1, Fizz1, YM1).
- SA suppressed MMT, decreasing α-SMA⁺CD68⁺ cells.
Conclusions:
- SA alleviates pulmonary fibrosis by inhibiting M2 macrophage polarization and MMT.
- SA shows promise as a therapeutic agent for pulmonary fibrosis.
