Aerobic Exercise Alleviates Inflammation, Oxidative Stress, and Apoptosis in Mice with Chronic Obstructive Pulmonary Disease

Abstract

Background

Chronic inflammation, oxidative stress, and apoptosis play critical roles in chronic obstructive pulmonary disease (COPD) pathogenesis. Here, we attempted to determine whether aerobic exercise (AE) could improve COPD by counteracting the COPD-associated inflammatory response, oxidative stress, and apoptosis in mice.

Methods

Thirty male ICR mice were assigned into one of three groups: control (Con), COPD, and COPD + AE. COPD was simulated by intratracheal injection of lipopolysaccharide (LPS) for 4 weeks. Low-intensity AE was performed for 4 weeks. Bronchoalveolar lavage fluid (BALF) cell counts and the levels of inflammatory cytokine in BALF and serum were detected. Hematoxylin and eosin (HE), Masson trichrome, and Sirius Red staining as well as terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to identify the degree of pulmonary emphysema, bronchial mucus cell hyperplasia, pulmonary fibrosis, and cell apoptosis. Oxidative stress parameters were measured. Furthermore, gene expression levels for the CXCL1, IL-1β, IL-10, IL-17, matrix metalloproteinase (MMP)9, TGF-β, TNF-α, and silent information regulator (sirt)1 were detected in mice lung tissues.

Results

AE improved LPS-induced emphysema, pulmonary fibrosis, bronchial mucus cell hyperplasia, bronchoconstriction, and cell apoptosis. AE prevented an LPS-induced increase in the total cell, neutrophil, and macrophage counts. AE decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels but increased glutathione (GSH) and superoxide dismutase (SOD) levels. AE decreased BALF levels of IL-1β, TNF-α, and TGF-β but increased BALF IL-10 levels. AE suppressed the gene expression levels of pro-inflammatory factors CXCL1, IL-1β, IL-17, and TNF-α and profibrotic factors MMP-9 and TGF-β but activated those of anti-inflammatory factor IL-10 and lung-protective factor sirt1.

Conclusion

AE is a potential therapeutic approach for COPD. AE improved emphysema, bronchial mucus cell hyperplasia, and pulmonary fibrosis in mice with COPD by alleviating the inflammatory response, oxidative stress injury, and cell apoptosis as well as activating sirt1.

Keywords:

• exercise
• COPD
• pulmonary fibrosis
• emphysema
• pulmonary inflammation
• oxidative stress injury

View correction statement:

Aerobic Exercise Alleviates Inflammation, Oxidative Stress, and Apoptosis in Mice with Chronic Obstructive Pulmonary Disease [Corrigendum]

Abbreviations

AE, aerobic exercise; COPD, chronic obstructive pulmonary disease; BALF, bronchoalveolar lavage fluid; HE, Hematoxylin and eosin; MDA, malondialdehyde; MPO, myeloperoxidase; GSH, glutathione; SOD, superoxide dismutase; IL, interleukin; TNF, tumor necrosis factor; CXCL, C-X-C motif chemokine ligand; TGF, transforming growth factor; MMP, matrix metalloproteinase; MLI, mean linear intercept; LPS, lipopolysaccharide; PFA, paraformaldehyde; sirt, silent information regulator; dUTP, terminal deoxynucleotidyl transferase; TUNEL, nick end labeling.

Data Sharing Statement

The datasets used or analyzed during the current study are available from the corresponding author Donghui Tang on reasonable request.

Acknowledgment

This study was supported by the National Natural Science Foundation of China (NSFC) (Grant No. 71874017, 81472992), the Agricultural Science and Technology Innovation Program (ASTIP) (cxgc-ias-01), and the BNU Interdisciplinary Research Foundation for the First-Year Doctoral Candidates (Grant No. BNUXKJC1814).

Disclosure

The authors report no conflicts of interest in this work, and the manuscript has been approved by all authors for publication.