Exercise Improves Lung Inflammation, but Not Lung Remodeling and Mechanics in a Model of Bleomycin-Induced Lung Fibrosis

在博来霉素诱发的肺纤维化模型中,运动可以改善肺部炎症,但不能改善肺部重塑和力学

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作者:Elias El-Mafarjeh, Gisele Henrique Cardoso Martins, Jessica Jorge Probst, Alana Santos-Dias, Manoel Carneiro Oliveira-Junior, Marcelo Paes de Barros, Luis Vicente Franco de Oliveira, Leandro Damas de Andrade, Renata Kelly da Palma, Renilson Moraes-Ferreira, Deborah de Camargo Hizume-Kunzler, André L

Conclusion

Aerobic exercise training initiated concomitantly with induction of pulmonary fibrosis reduces lung and systemic inflammation but fails to inhibit lung fibrosis and mechanics impairment.

Methods

C57Bl/6 mice were distributed into four groups: Control (Co), Exercise (Exe), Bleomycin (Bleo), and Bleomycin+Exercise (Bleo+Exe). A single bleomycin dose (1.5 UI/kg) was administered orotracheally and treadmill exercise started in the same day, enduring for 4 weeks, 5x/week, 60 minutes/session, at moderate intensity. Lung mechanics, systemic and pulmonary inflammation, and lung remodeling were evaluated. Lung homogenates were used to evaluate the antioxidant status.

Results

Total cells, macrophages, lymphocytes, and neutrophils numbers, in agreement with IL-6 levels, were higher in the BAL and serum of Bleo group, compared to other groups. In addition, lung levels of LTB4 in Bleo were higher than other groups, whereas SOD activity and nitric oxide levels in exercised groups (Exe and Exe+Bleo) compared to the Bleo group. Lung GPX activity was lower in Bleo and Exe+Bleo groups compared to others. Exe and Exe+Bleo groups also showed higher IL-10 expression by lung macrophages than other groups, whereas TGF-β expression was higher in Exe, Bleo, and Exe+Bleo groups compared to control. CCR7 expression was induced only in the Exe group. However, exercise did not improve lung remodeling and mechanics, or serum and pulmonary levels of VEGF, IGF-1, and TGF-β.

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