Simoes Davina C M, Vogiatzis Ioannis
Department of Applied Sciences, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, UK.
Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne, UK.
J Thorac Dis. 2018 May;10(Suppl 12):S1367-S1376. doi: 10.21037/jtd.2018.02.67.
Patients with stable chronic obstructive pulmonary disease (COPD) frequently exhibit unintentional accentuated peripheral muscle loss and dysfunction. Skeletal muscle mass in these patients is a strong independent predictor of morbidity and mortality. Factors including protein anabolism/catabolism imbalance, hypoxia, physical inactivity, inflammation, and oxidative stress are involved in the initiation and progression of muscle wasting in these patients. Exercise training remains the most powerful intervention for reversing, in part, muscle wasting in COPD. Independently of the status of systemic or local muscle inflammation, rehabilitative exercise training induces up-regulation of key factors governing skeletal muscle hypertrophy and regeneration. However, COPD patients presenting similar degrees of lung dysfunction do not respond alike to a given rehabilitative exercise stimulus. In addition, a proportion of patients experience limited clinical outcomes, even when exercise training has been adequately performed. Consistently, several reports provide evidence that the muscles of COPD patients present training-induced myogenic activity limitation as exercise training induces a limited number of differentially expressed genes, which are mostly associated with protein degradation. This review summarises the nature of muscle adaptations induced by exercise training, promoted both by changes in the expression of contractile proteins and their function typically controlled by intracellular signalling and transcriptional responses. Rehabilitative exercise training in COPD patients stimulates skeletal muscle mechanosensitive signalling pathways for protein accretion and its regulation during muscle contraction. Exercise training also induces synthesis of myogenic proteins by which COPD skeletal muscle promotes hypertrophy leading to fusion of myogenic cells to the myofiber. Understanding of the biological mechanisms that regulate exercise training-induced muscle growth and regeneration is necessary for implementing therapeutic strategies specifically targeting myogenesis and hypertrophy in these patients.
稳定期慢性阻塞性肺疾病（COPD）患者常出现非故意性的外周肌肉加速流失和功能障碍。这些患者的骨骼肌质量是发病率和死亡率的强有力独立预测指标。包括蛋白质合成代谢/分解代谢失衡、缺氧、身体活动不足、炎症和氧化应激等因素参与了这些患者肌肉萎缩的起始和进展过程。运动训练仍然是部分逆转COPD患者肌肉萎缩的最有效干预措施。无论全身或局部肌肉炎症状态如何，康复运动训练都会诱导调控骨骼肌肥大和再生的关键因子上调。然而，具有相似程度肺功能障碍的COPD患者对给定的康复运动刺激反应并不相同。此外，即使运动训练已充分进行，仍有一部分患者的临床效果有限。一致地，一些报告提供证据表明，COPD患者的肌肉在运动训练时表现出成肌活性受限，因为运动训练诱导的差异表达基因数量有限，且大多与蛋白质降解相关。本综述总结了运动训练诱导的肌肉适应性本质，这是由收缩蛋白表达变化及其功能所促进的，而收缩蛋白功能通常由细胞内信号传导和转录反应控制。COPD患者的康复运动训练会刺激骨骼肌机械敏感信号通路，以促进肌肉收缩过程中的蛋白质积累及其调节。运动训练还会诱导成肌蛋白的合成，通过这种方式，COPD患者的骨骼肌促进肥大，导致成肌细胞与肌纤维融合。了解调节运动训练诱导的肌肉生长和再生的生物学机制，对于实施专门针对这些患者的肌生成和肥大的治疗策略是必要的。
