Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress
Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress
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DOI：
10.1210/jc.2006-0651
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发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Ferrando, Arny A.
中科院分区：
文献类型：
--
作者：
Paddon-Jones, Douglas;Sheffield-Moore, Melinda;Ferrando, Arny A.
背景：我们最近证明，健康志愿者28天卧床休息会导致瘦腿质量和力量的适度下降。目的：本研究的目的是量化临床卧床休息模型中肌肉蛋白质动力学、身体成分和力量的变化，该模型既反映了身体缺乏活动，也反映了对损伤或疾病的荷尔蒙应激反应。设计：计算肌肉蛋白质动力学，研究地点：德克萨斯大学医学院综合临床研究中心。参与者：健康男性志愿者(n=6，28+/-2，84+/-4 kg，178+/-3 cm)。干预：卧床期间，给予氢化可的松琥珀酸钠静脉注射(d1和28)和口服(d2-27)，以复制与创伤或疾病相一致的血浆皮质醇浓度(类似于22mug/dl)。主要观察指标：我们假设不活动和高皮质醇血症会减少瘦肌肉质量，腿部伸展力量，结果：与我们以前的卧床休息模式相比，志愿者的腿部伸展力量下降了28.4%/-4.4%(P=0.012)，瘦腿质量下降了3倍(1.4%/-0.1kgP=0.004)。蛋白质的净分解代谢主要是由于肌肉蛋白质合成的减少[分数合成率，0.081+/-0.004(D1)vs.0.054+/-0.007%/h(D28)；P=0.023]。肌肉蛋白质分解没有变化。结论：长期不活动和高皮质醇血症是一种持续性分解代谢刺激，通过肌肉蛋白质合成的慢性减少加剧力量和瘦肉损失。
Context: We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength.Objective: The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness.Design: Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 mu mol/kg center dot min) of C-13(6)-phenylalanine on d 1 and 28 of bed rest.Setting: The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch.Participants: Participants were healthy male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm).Intervention: During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with trauma or illness (similar to 22 mu g/dl).Main Outcome Measures: We hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass, leg extension strength, and muscle protein synthesis.Results: Volunteers experienced a 28.4 +/- 4.4% loss of leg extension strength (P = 0.012) and a 3-fold greater loss of lean leg mass (1.4 +/- 0.1 kg) (P = 0.004) compared with our previous bed rest-only model. Net protein catabolism was primarily due to a reduction in muscle protein synthesis [fractional synthesis rate, 0.081 +/- 0.004 (d 1) vs. 0.054 +/- 0.007%/h (d 28); P = 0.023]. There was no change in muscle protein breakdown.Conclusion: Prolonged inactivity and hypercortisolemia represents a persistent catabolic stimulus that exacerbates strength and lean muscle loss via a chronic reduction in muscle protein synthesis.