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Background <p>Pulmonary fibrosis is a chronic and progressive lung disease with limited therapeutic options. This study aimed to investigate the roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats.</p> Methods <p>Male Sprague–Dawley rats were randomly assigned to five groups: Sham (SHAM; intratracheal [I.T.] saline), bleomycin (BLM; 2&#xa0;mg/kg, I.T.), bleomycin with right cervical vagotomy (BLVR), bleomycin with nicotine (0.5&#xa0;mg/kg/day, intraperitoneal [I.P.]) (BLNC), and bleomycin with vagotomy plus nicotine (BLVN).</p> Results <p>Twenty-four hours after bleomycin or saline administration, total white blood cell (WBC) counts and the neutrophil-to-lymphocyte ratio (NLR) increased in all groups, with the BLVR group exhibiting significantly higher values than the BLM, BLNC, and BLVN groups. On day 14, NLR in the BLVR group and WBC counts in the BLM and BLVR groups remained elevated. Lung malondialdehyde levels were higher in the BLM and BLVR groups compared with the BLNC and BLVN groups. During mechanical ventilation, peak expiratory pressures were higher in the BLM, BLVR, and BLNC groups than in the SHAM group, whereas the BLVN group showed values comparable to the SHAM group. Lung compliance was lowest in the BLVR group but was preserved in the BLVN group. Histopathological examination confirmed reduced lung injury in the BLVN group compared with the BLM and BLVR groups.</p> Conclusions <p>These findings highlight the anti-inflammatory role of the vagus nerve and suggest that nicotine—particularly in combination with vagotomy—may confer protective effects against early-stage pulmonary fibrosis by mitigating inflammation, oxidative stress, and pulmonary dysfunction.</p>

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Modulatory roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Parisa Askarizadeh,
  • Amirreza Dehghanian,
  • Farzaneh Ketabchi

摘要

Background

Pulmonary fibrosis is a chronic and progressive lung disease with limited therapeutic options. This study aimed to investigate the roles of the vagus nerve and nicotine in bleomycin-induced pulmonary fibrosis in rats.

Methods

Male Sprague–Dawley rats were randomly assigned to five groups: Sham (SHAM; intratracheal [I.T.] saline), bleomycin (BLM; 2 mg/kg, I.T.), bleomycin with right cervical vagotomy (BLVR), bleomycin with nicotine (0.5 mg/kg/day, intraperitoneal [I.P.]) (BLNC), and bleomycin with vagotomy plus nicotine (BLVN).

Results

Twenty-four hours after bleomycin or saline administration, total white blood cell (WBC) counts and the neutrophil-to-lymphocyte ratio (NLR) increased in all groups, with the BLVR group exhibiting significantly higher values than the BLM, BLNC, and BLVN groups. On day 14, NLR in the BLVR group and WBC counts in the BLM and BLVR groups remained elevated. Lung malondialdehyde levels were higher in the BLM and BLVR groups compared with the BLNC and BLVN groups. During mechanical ventilation, peak expiratory pressures were higher in the BLM, BLVR, and BLNC groups than in the SHAM group, whereas the BLVN group showed values comparable to the SHAM group. Lung compliance was lowest in the BLVR group but was preserved in the BLVN group. Histopathological examination confirmed reduced lung injury in the BLVN group compared with the BLM and BLVR groups.

Conclusions

These findings highlight the anti-inflammatory role of the vagus nerve and suggest that nicotine—particularly in combination with vagotomy—may confer protective effects against early-stage pulmonary fibrosis by mitigating inflammation, oxidative stress, and pulmonary dysfunction.