危重病早期骨骼肌的代谢表型。

Metabolic phenotype of skeletal muscle in early critical illness.

机构信息

Institute for Sport, Exercise and Health, University College London, London, UK.

Department of Medicine, Centre for Human Health and Performance, University College London, London, UK.

出版信息

Thorax. 2018 Oct;73(10):926-935. doi: 10.1136/thoraxjnl-2017-211073. Epub 2018 Jul 6.

DOI:10.1136/thoraxjnl-2017-211073

PMID:29980655

Abstract

OBJECTIVES

To characterise the sketetal muscle metabolic phenotype during early critical illness.

METHODS

Vastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5).

MEASUREMENTS AND MAIN RESULTS

From day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (-27.4CN (95% CI -123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (-1859CN (IQR -5557-1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (-4.8 mmol/kg dw (IQR -8.0-1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR -0.09-2.6); n=31; p<0.001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5-1672); n=15; p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR -0.44-3.33); n=29; p=0.041) and IL-10 (13.6 ng (IQR 3.4-39.0); n=29; p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7); p<0.001) and ghrelin (16.0 ng/mL (IQR -7-100); p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered.

CONCLUSIONS

Decreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting.

TRIAL REGISTRATION NUMBER

NCT01106300.

摘要

目的

描述早期危重病期间骨骼肌代谢表型。

方法

从 63 名重症监护患者（59%男性，54.7±18.0 岁，急性生理学和慢性健康评估 II 评分 23.5±6.5）中获得股外侧肌活检和血清样本（第 1 天和第 7 天）。

测量和主要结果

从第 1 天到第 7 天，线粒体β氧化酶浓度、线粒体生物发生标志物（PGC1α信使 mRNA 表达减少 27.4CN（95%CI-123.9 至 14.3）；n=23；p=0.025）和线粒体 DNA 拷贝数减少 1859CN（IQR-5557-1325）；n=35；p=0.032）。与对照组相比，第 1 天股外侧肌的肌内 ATP 含量降低（17.7mmol/kg /干重（dw）（95%CI 15.3 至 20.0）与 21.7 mmol/kg/dw（95%CI 20.4 至 22.9）；p<0.001），并且在 7 天内下降（-4.8 mmol/kg dw（IQR-8.0-1.2）；n=33；p=0.001）。此外，磷酸化：总 AMP-K（生物能传感器）的比值增加（0.52（IQR-0.09-2.6）；n=31；p<0.001）。肌内磷酸胆碱增加（847.2AU（IQR 232.5-1672）；n=15；p=0.022），肌内肿瘤坏死因子受体 1（0.66μg（IQR-0.44-3.33）；n=29；p=0.041）和 IL-10（13.6ng（IQR 3.4-39.0）；n=29；p=0.004）增加。血清脂联素（10.3μg（95%CI 6.8 至 13.7）；p<0.001）和 ghrelin（16.0ng/ml（IQR-7-100）；p=0.028）增加。网络分析显示，生物能障碍与肌肉减少之间以及肌肉内炎症与合成代谢信号受损之间存在密切和直接的关系。ATP 含量和肌肉量与脂质输送无关。