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已发表论文
mTOR 抑制剂雷帕霉素减轻小鼠臭氧诱导的气道炎症和肺气肿
Authors Tian X , Han L, Huang Y , Zhou Y, Zhang X , Zhang M
Received 12 June 2025
Accepted for publication 10 October 2025
Published 4 February 2026 Volume 2026:19 545564
DOI https://doi.org/10.2147/JIR.S545564
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Yuhan Xing
Xue Tian,* Lei Han,* Yuning Huang,* Yan Zhou, Xue Zhang, Min Zhang
Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Min Zhang, Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China, Email zhangmin@sjtu.edu.cn Xue Zhang, Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China, Email zx15800562053@163.com
Background: Ozone exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). In this study, we investigated the potential role of targeting mTOR signaling in the treatment of COPD induced by ozone exposure.
Methods: The public database was chosen to explore the expression of mTOR mRNA, S6K1 mRNA, and LC3B mRNA in COPD patients, and potential correlations with FEV1(%pred). In an ozone-exposed mouse model, large airway and small airway function were evaluated by spirometry. After intraperitoneal injection of a mTOR inhibitor known as rapamycin, the emphysema index, and inflammation scores in lung tissue were measured. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and levels of cytokines in the lung tissue were also observed. Airway remodeling in the lung tissue was detected using Masson’s trichrome stains and immunohistochemical staining. Mucus hypersecretion was evaluated by PAS staining. The protein expression of the mTOR pathway and autophagy marker LC3B in the lung tissue was determined through Western blot.
Results: mTOR mRNA and S6K1 mRNA were upregulated in patients with COPD compared to the control subjects, whereas LC3B mRNA showed a downward shift in patients with COPD. Mice that received mTOR inhibitor treatment displayed higher FEV50/FVC, FEF25, FEF50, FEF75, and MMEF. The mTOR inhibitor rapamycin improved the emphysema index and inflammation scores in mice lung tissue. Moreover, it significantly inhibited inflammatory cell infiltration in BALF, IL-1β, TNF-α, and NF-κb in the lung tissue of ozone-exposed mice. The mTOR inhibitor significantly suppressed mucus hypersecretion in large and small airways and decreased the protein expression of collagen I and α-SMA in the lung tissue of ozone-exposed mice. Notably, mTOR repression also decreased the protein expression of S6K1 and increased LC3B expression in the lung tissue.
Conclusion: The mTOR inhibitor rapamycin ameliorates ozone-induced airway inflammation and emphysema in a LC3B-dependent manner. mTOR inhibition may offer a promising therapeutic approach for preventing ozone-induced COPD by mitigating airway inflammation, reducing airway remodeling, and alleviating mucus hypersecretion.
Keywords: chronic obstructive pulmonary disease, mTOR pathway, rapamycin, airway inflammation, emphysema
Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Min Zhang, Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China, Email zhangmin@sjtu.edu.cn Xue Zhang, Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China, Email zx15800562053@163.com
Background: Ozone exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). In this study, we investigated the potential role of targeting mTOR signaling in the treatment of COPD induced by ozone exposure.
Methods: The public database was chosen to explore the expression of mTOR mRNA, S6K1 mRNA, and LC3B mRNA in COPD patients, and potential correlations with FEV1(%pred). In an ozone-exposed mouse model, large airway and small airway function were evaluated by spirometry. After intraperitoneal injection of a mTOR inhibitor known as rapamycin, the emphysema index, and inflammation scores in lung tissue were measured. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and levels of cytokines in the lung tissue were also observed. Airway remodeling in the lung tissue was detected using Masson’s trichrome stains and immunohistochemical staining. Mucus hypersecretion was evaluated by PAS staining. The protein expression of the mTOR pathway and autophagy marker LC3B in the lung tissue was determined through Western blot.
Results: mTOR mRNA and S6K1 mRNA were upregulated in patients with COPD compared to the control subjects, whereas LC3B mRNA showed a downward shift in patients with COPD. Mice that received mTOR inhibitor treatment displayed higher FEV50/FVC, FEF25, FEF50, FEF75, and MMEF. The mTOR inhibitor rapamycin improved the emphysema index and inflammation scores in mice lung tissue. Moreover, it significantly inhibited inflammatory cell infiltration in BALF, IL-1β, TNF-α, and NF-κb in the lung tissue of ozone-exposed mice. The mTOR inhibitor significantly suppressed mucus hypersecretion in large and small airways and decreased the protein expression of collagen I and α-SMA in the lung tissue of ozone-exposed mice. Notably, mTOR repression also decreased the protein expression of S6K1 and increased LC3B expression in the lung tissue.
Conclusion: The mTOR inhibitor rapamycin ameliorates ozone-induced airway inflammation and emphysema in a LC3B-dependent manner. mTOR inhibition may offer a promising therapeutic approach for preventing ozone-induced COPD by mitigating airway inflammation, reducing airway remodeling, and alleviating mucus hypersecretion.
Keywords: chronic obstructive pulmonary disease, mTOR pathway, rapamycin, airway inflammation, emphysema