Vanhorebeek Ilse, Gunst Jan, Casaer Michaël P, Derese Inge, Derde Sarah, Pauwels Lies, Segers Johan, Hermans Greet, Gosselink Rik, Van den Berghe Greet
Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Clinical Division of Intensive Care Medicine, University Hospitals Leuven, 3000 Leuven, Belgium.
J Endocr Soc. 2023 Jan 5;7(3):bvad001. doi: 10.1210/jendso/bvad001. eCollection 2023 Jan 6.
Muscle expresses and secretes several myokines that bring about benefits in distant organs.
We investigated the impact of critical illness on muscular expression of irisin, kynurenine aminotransferases, and amylase; association with clinical outcome; and impact of interventions that attenuate muscle wasting/weakness.
We studied critically ill patients who participated in 2 randomized controlled trials (EPaNIC/NESCI) and documented time profiles in critically ill mice. Included in the study were 174 intensive care unit (ICU) patients (day 8 ± 1) vs 19 matched controls, and 60 mice subjected to surgery/sepsis vs 60 pair-fed healthy mice. Interventions studied included 7-day neuromuscular electrical stimulation (NMES), and withholding parenteral nutrition (PN) in the first ICU week (late PN) vs early PN. The main outcome measures were (irisin- precursor), , and amylase mRNA expression in skeletal muscle.
Critically ill patients showed 34% to 80% lower mRNA expression of , , and amylases than controls ( < .0001). Critically ill mice showed time-dependent reductions in all mRNAs compared with healthy mice ( ≤ .04). The lower expression in patients was independently associated with a higher ICU mortality ( = .015) and ICU-acquired weakness ( = .012), whereas the lower amylase expression in ICU survivors was independently associated with a longer ICU stay ( = .0060). Lower amylase expression was independently associated with a lower risk of death ( = .048), and lower expression with a lower risk of weakness ( = .022). NMES increased expression compared with unstimulated muscle ( = .016), and late PN patients had a higher expression than early PN patients ( = .022).
Expression of the studied myokines was affected by critical illness and associated with clinical outcomes, with limited effects of interventions that attenuate muscle wasting or weakness.
肌肉表达并分泌多种对远处器官有益的肌动蛋白。
我们研究了危重病对鸢尾素、犬尿氨酸转氨酶和淀粉酶肌肉表达的影响；与临床结局的关联；以及减轻肌肉萎缩/无力的干预措施的影响。
我们研究了参与两项随机对照试验（EPaNIC/NESCI）的危重病患者，并记录了危重病小鼠的时间变化情况。研究纳入了174名重症监护病房（ICU）患者（第8天±1天）与19名匹配的对照组，以及60只接受手术/脓毒症的小鼠与60只成对喂养的健康小鼠。研究的干预措施包括7天的神经肌肉电刺激（NMES），以及在ICU第一周停用肠外营养（PN）（延迟PN）与早期PN。主要结局指标是骨骼肌中鸢尾素（鸢尾素前体）、犬尿氨酸转氨酶和淀粉酶的mRNA表达。
危重病患者的鸢尾素、犬尿氨酸转氨酶和淀粉酶的mRNA表达比对照组低34%至80%（P<0.0001）。与健康小鼠相比，危重病小鼠的所有mRNA均呈现时间依赖性降低（P≤0.04）。患者中较低的鸢尾素表达与较高的ICU死亡率（P=0.015）和ICU获得性肌无力（P=0.012）独立相关，而ICU幸存者中较低的淀粉酶表达与较长的ICU住院时间独立相关（P=0.0060）。较低的淀粉酶表达与较低的死亡风险独立相关（P=0.048），较低的鸢尾素表达与较低的肌无力风险独立相关（P=0.022）。与未刺激的肌肉相比，NMES增加了鸢尾素的表达（P=0.016），延迟PN患者的鸢尾素表达高于早期PN患者（P=0.022）。
所研究的肌动蛋白的表达受危重病影响，并与临床结局相关，减轻肌肉萎缩或无力的干预措施效果有限。
