No abstract

Background: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. Methods: Sprague-Dawley rats were classified into five groups: non-COPD/rest (n = 8), non-COPD/exercise (n = 7), COPD/rest (n = 7), COPD/medium exercise (n = 10), and COPD/intensive exercise (n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/ exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5°and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5°and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflowassisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ± 15.33 g (P = 0.0005). The oxidative muscle fibers proportion was lower (P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (D58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (D0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (D0.06 mm, 95% CI: 0.02-0.10 mm, P = 0.006), oxidative muscle fiber percentage (D4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity (P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.