MRC/ARUK Centre for Musculoskeletal Ageing Research, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
Thorax. 2013 Jul;68(7):625-33. doi: 10.1136/thoraxjnl-2012-202764. Epub 2013 Mar 27.
Skeletal muscle dysfunction is a systemic feature of chronic obstructive pulmonary disease (COPD), contributing to morbidity and mortality. Physical training improves muscle mass and function in COPD, but the molecular regulation therein is poorly understood.
Candidate genes and proteins regulating muscle protein breakdown (ubiquitin proteasome pathway), muscle protein synthesis (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway), myogenesis (MyoD, myogenin and myostatin) and transcription (FOXO1, FOXO3 and RUNX1) were determined in quadriceps muscle samples taken at four time points over 8 weeks of knee extensor resistance training (RT) in patients with COPD and healthy controls (HCs). Patients with COPD were randomly allocated to receive protein/carbohydrate or placebo supplements during RT.
59 patients with COPD (mean (SD) age 68.0 (9.3) years, forced expiratory volume in 1 s (FEV1) 46.9 (17.8) % predicted) and 21 HCs (66.1 (4.8) years, 105.0 (21.6) % predicted) were enrolled. RT increased lean mass (5%) and strength (20%) in all groups. Absolute work done during RT was lower throughout in patients with COPD compared with HCs. RT resulted in increases (from basal) in catabolic, anabolic, myogenic and transcription factor protein expression at 24 h, 4 weeks and 8 weeks of exercise in HCs. This response was blunted in patients with COPD, except for myogenic signalling, which was similar. Nutritional supplementation did not augment functional or molecular responses to RT.
The potential for muscle rehabilitation in response to RT is preserved in COPD. Except for markers of myogenesis, molecular responses to RT are not tightly coupled to lean mass gains but reflect the lower work done during RT, suggesting some caution when identifying molecular targets for intervention. Increasing post-exercise protein and carbohydrate intake is not a prerequisite for a normal training response in COPD.
骨骼肌功能障碍是慢性阻塞性肺疾病（COPD）的一个全身特征，导致发病率和死亡率增加。身体训练可改善 COPD 患者的肌肉质量和功能，但其中的分子调节机制尚不清楚。
在 COPD 患者和健康对照者（HCs）接受 8 周膝关节伸肌抗阻训练（RT）的 4 个时间点，从股四头肌样本中确定调节肌肉蛋白分解（泛素蛋白酶体途径）、肌肉蛋白合成（磷酸肌醇 3 激酶/Akt/雷帕霉素靶蛋白途径）、成肌（MyoD、myogenin 和 myostatin）和转录（FOXO1、FOXO3 和 RUNX1）的候选基因和蛋白。将 COPD 患者随机分为接受蛋白质/碳水化合物或安慰剂补充剂在 RT 期间。
共纳入 59 例 COPD 患者（平均年龄（标准差）68.0（9.3）岁，用力呼气量 1 秒（FEV1）占预计值的 46.9（17.8）%）和 21 例 HCs（66.1（4.8）岁，105.0（21.6）%预计值）。所有组的 RT 均增加了瘦体重（5%）和力量（20%）。与 HCs 相比，COPD 患者在整个 RT 期间的绝对做功均较低。在 HCs 中，RT 在运动后 24 小时、4 周和 8 周时，导致分解代谢、合成代谢、成肌和转录因子蛋白表达增加（与基础值相比）。这种反应在 COPD 患者中减弱，除了成肌信号，其反应相似。营养补充并没有增强对 RT 的功能或分子反应。
COPD 患者对 RT 的肌肉康复潜力是存在的。除了成肌标志物外，RT 的分子反应与瘦体重增加没有紧密耦合，而是反映了 RT 期间较低的做功，因此在确定干预的分子靶点时需要谨慎。增加运动后蛋白质和碳水化合物的摄入并不是 COPD 正常训练反应的必要条件。
