Department of Sports Medicine, Shanghai University of Sport, Shanghai 200438, P.R. China.
School of Physical Education and Sport Training, Shanghai University of Sport, Shanghai 200438, P.R. China.
Int J Mol Med. 2020 Jun;45(6):1644-1660. doi: 10.3892/ijmm.2020.4537. Epub 2020 Mar 12.
Decreased diaphragm function is a crucial factor leading to reduced ventilatory efficiency and worsening of quality of life in chronic obstructive pulmonary disease (COPD). Exercise training has been demonstrated to effectively improve the function of the diaphragm. However, the mechanism of this process has not been identified. The emergence of metabolomics has allowed the exploration of new ideas. The present study aimed to analyze the potential biomarkers of exercise‑dependent enhancement of diaphragm function in COPD using metabolomics. Sprague Dawley rats were divided into three groups: COPD + exercise group (CEG); COPD model group (CMG); and control group (CG). The first two groups were exposed to cigarette smoke for 16 weeks to establish a COPD model. Then, the rats in the CEG underwent aerobic exercise training for 9 weeks. Following confirmation that exercise effectively improved the diaphragm function, a gas chromatography tandem time‑of‑flight mass spectrometry analysis system was used to detect the differential metabolites and associated pathways in the diaphragm muscles of the different groups. Following exercise intervention, the pulmonary function and diaphragm contractility of the CEG rats were significantly improved compared with those of the CMG rats. A total of 36 different metabolites were identified in the comparison between the CMG and the CG. Pathway enrichment analysis indicated that these different metabolites were involved in 17 pathways. A total of 29 different metabolites were identified in the comparison between the CMG and the CEG, which are involved in 14 pathways. Candidate biomarkers were selected, and the pathways analysis of these metabolites demonstrated that 2 types of metabolic pathways, the nicotinic acid and nicotinamide metabolism and arginine and proline metabolism pathways, were associated with exercise‑induced pulmonary rehabilitation.
膈肌功能下降是导致慢性阻塞性肺疾病（COPD）患者通气效率降低和生活质量恶化的关键因素。运动训练已被证实能有效改善膈肌功能。然而，这一过程的机制尚未确定。代谢组学的出现为探索新的思路提供了可能。本研究旨在利用代谢组学分析 COPD 患者运动依赖性膈肌功能增强的潜在生物标志物。将 Sprague Dawley 大鼠分为三组：COPD+运动组（CEG）；COPD 模型组（CMG）；对照组（CG）。前两组大鼠暴露于香烟烟雾中 16 周以建立 COPD 模型。然后，CEG 组大鼠进行 9 周有氧运动训练。在确认运动有效改善膈肌功能后，使用气相色谱串联飞行时间质谱分析系统检测不同组膈肌肌肉中的差异代谢物和相关途径。运动干预后，CEG 组大鼠的肺功能和膈肌收缩力明显优于 CMG 组。CMG 与 CG 比较，共鉴定出 36 种不同的代谢物。途径富集分析表明，这些不同的代谢物涉及 17 条途径。CMG 与 CEG 比较，共鉴定出 29 种不同的代谢物，涉及 14 条途径。选择候选生物标志物，并对这些代谢物的途径分析表明，2 种代谢途径，即烟酸和烟酰胺代谢途径以及精氨酸和脯氨酸代谢途径，与运动诱导的肺康复有关。
