The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition. A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated. MSTN gene expression (median [IQR] fold change: 1.00 [0.68–1.54] vs. 0.26 [0.11–0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways. Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients. Trial registration: ISRCTN77569430 —13th of February 2008 and ISRCTN19392591 17th of February 2011.

中文翻译：

---

重症患者肌肉肌生长抑制素基因表达和血浆浓度降低

目的是研究基因表达和肌肉蛋白肌肉生长抑制素血浆水平在重症监护病房获得性虚弱 (ICUAW) 中的作用。这是为了评估治疗性肌生长抑制素抑制的潜在临床和/或病理生理学原理。对两项前瞻性研究的汇总数据进行了回顾性分析，以评估肌肉生长抑制素血浆浓度（第 4 天、第 8 天和第 14 天）和骨骼肌中肌肉生长抑制素基因 (MSTN) 表达水平（第 15 天）的动态。研究了肌肉生长抑制素与临床和电生理结果、肌肉代谢和肌肉萎缩途径的关联。MSTN 基因表达（中位数 [IQR] 倍数变化：1.00 [0.68–1.54] vs. 0.26 [0.11–0.80]；p = 0。004) 和肌肉生长抑制素血浆浓度在所有危重病人中与健康对照组相比显着降低。在重症患者中，肌肉生长抑制素血浆浓度随时间增加（中位 [IQR] 倍数变化：第 4 天：0.13 [0.08/0.21] 对比第 8 天：0.23 [0.10/0.43] 对比第 14 天：0.40 [0.26/0.61] ; p < 0.001)。ICUAW 患者与未 ICUAW 患者相比，MSTN 基因表达水平显着降低（中位数 [IQR] 倍数变化：0.17 [0.10/0.33] 和 0.51 [0.20/0.86]；p = 0.047）。肌肉生长抑制素水平与肌肉力量（相关系数 0.339；p = 0.020）和胰岛素敏感性指数（相关系数 0.357；p = 0.015）直接相关。未观察到肌生长抑制素血浆浓度以及 MSTN 表达水平和动员水平、电生理变量、或萎缩途径的标志物。在危重病期间，肌肉基因表达和肌肉抑制素的全身蛋白水平下调。因此，先前提出的对肌肉生长抑制素的治疗性抑制似乎没有改善危重患者肌肉质量的病理生理学原理。试用注册：ISRCTN77569430 — 2008 年 2 月 13 日和 ISRCTN19392591 2011 年 2 月 17 日。