Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13357, Berlin, Germany.
Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Crit Care. 2022 Aug 3;26(1):237. doi: 10.1186/s13054-022-04101-1.
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.
ISRCTN77569430 -13th of February 2008 and ISRCTN19392591 17th of February 2011.
本研究旨在探讨肌肉蛋白生长抑素（myostatin）在重症监护病房获得性肌无力（ICUAW）中的作用。这是为了评估治疗性生长抑素抑制的潜在临床和/或病理生理依据。
对两项前瞻性研究的汇总数据进行回顾性分析，以评估肌肉生长抑素（myostatin）在第 4、8 和 14 天的血浆浓度（第 4、8 和 14 天）和第 15 天骨骼肌中的生长抑素基因（MSTN）表达水平的变化。研究了生长抑素与临床和电生理结果、肌肉代谢和肌肉萎缩途径的关系。
与健康对照组相比，所有危重病患者的 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）和肌肉生长抑素血浆浓度均显著降低。在危重病患者中，肌肉生长抑素的血浆浓度随时间增加（中位数[IQR]倍数变化：第 4 天：0.13[0.08/0.21] vs. 第 8 天：0.23[0.10/0.43] vs. 第 14 天：0.40[0.26/0.61]；p<0.001）。与无 ICUAW 的患者相比，有 ICUAW 的患者 MSTN 基因表达水平显著降低（中位数[IQR]倍数变化：0.17[0.10/0.33]和 0.51[0.20/0.86]；p=0.047）。生长抑素水平与肌肉力量直接相关（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）。未观察到肌肉生长抑素血浆浓度以及 MSTN 表达水平与动员水平、电生理变量或萎缩途径标志物之间存在相关性。
在危重病期间，肌肉基因表达和全身肌肉生长抑素蛋白水平下调。因此，先前提出的肌肉生长抑素的治疗性抑制似乎没有改善危重病患者肌肉质量的病理生理依据。
ISRCTN77569430-2008 年 2 月 13 日和 ISRCTN19392591-2011 年 2 月 17 日。
