Inactivity amplifies the catabolic response of skeletal muscle to cortisol
Inactivity amplifies the catabolic response of skeletal muscle to cortisol
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DOI：
10.1210/jc.84.10.3515
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发表时间：
1999-10-01
影响因子：
5.8
通讯作者：
Wolfe, RR
中科院分区：
文献类型：
--
作者：
Ferrando, AA;Stuart, CA;Wolfe, RR
严重损伤或创伤伴随着高皮质醇血症和长时间不活动或卧床休息（BR）。创伤和 BR 单独导致肌肉氮的损失，尽管通过不同的代谢改变。虽然单独使用 BR 会导致去脂体重减少 2-3%，但严重创伤的影响可能会增加 2-3 倍。我们研究了高皮质醇血症和长期不活动对健康志愿者肌肉蛋白质代谢的综合影响。使用基于动静脉取样和肌肉活检的模型对 6 名男性进行了 14 天严格 BR 前后的研究。还直接计算骨骼肌蛋白的合成分数和分解率。每次蛋白质代谢评估均在输注氢化可的松琥珀酸钠（120μg/kg.h）12小时期间进行，导致血液皮质醇浓度模拟严重损伤（约31μg/dL）。经过 14 天的严格 BR 治疗后，高皮质醇血症使肌肉中的苯丙氨酸流出量增加了 3 倍（P < 0.05）。负氨基酸平衡的增强是肌肉蛋白质分解增加的结果（P < 0.05），但肌肉蛋白质合成没有伴随变化。由于从头合成显着增加，卧床休息后谷氨酰胺和丙氨酸的肌肉流出显着增加（P < 0.05）。因此，不活动会使骨骼肌对高皮质醇血症的分解代谢作用敏感。此外，这些对健康志愿者的影响与严重受伤后的影响类似。
Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 mu g/kg.h), resulting in blood cortisol concentrations that mimic severe injury (approximate to 31 mu g/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.