Intensive Care Unit Acquired Weakness Is Associated with Rapid Changes to Skeletal Muscle Proteostasis.
Intensive Care Unit Acquired Weakness Is Associated with Rapid Changes to Skeletal Muscle Proteostasis.
复制标题
重症监护病房获得性虚弱与骨骼肌蛋白稳态的快速变化有关。
作者：
重症监护病房 (ICU) 获得性无力是影响肢体和呼吸肌的危重疾病的常见后果。 ICU获得性肌无力的原因是多因素的，但长期肢体肌肉不活动和机械通气都是肌肉萎缩的危险因素，这使ICU患者容易出现因肌无力而导致的短期并发症和长期残疾。不幸的是，目前的研究并没有提供对 ICU 获得性无力的细胞病因学的详细了解，也没有标准的治疗方法。因此，提高对危重患者肌肉萎缩机制的了解对于制定预防 ICU 引起的骨骼肌萎缩的治疗策略至关重要。为了加深我们对 ICU 获得性无力的机制的理解，我们测试了这样的假设：ICU 引起的肌肉不活动会促进合成代谢信号/蛋白质合成的快速减少，并加速肢体和呼吸肌的蛋白水解。为了研究 ICU 诱导的骨骼肌蛋白质稳态变化，将成年 Sprague Dawley 大鼠麻醉并机械通气 12 小时以模拟 ICU 护理。对四肢肌肉（跖肌和比目鱼肌）和呼吸肌（胸骨旁和肋间）的合成代谢信号、蛋白质合成和蛋白水解活性的测量显示，ICU 诱导的合成代谢信号（即 AKT/mTOR 途径）和肌肉蛋白质合成均减少。此外，模拟 ICU 护理导致肢体和呼吸肌中加速蛋白水解的生物标志物增加。这些新发现表明，无论肌肉功能或肌纤维类型如何，在 ICU 引起的肌肉不活动期间，肢体和呼吸肌蛋白质稳态的紊乱都会迅速发生。
Intensive care unit (ICU)-acquired weakness is a frequent consequence of critical illness that impacts both the limb and respiratory muscles. The cause of ICU-acquired weakness is multifactorial, but both prolonged limb muscle inactivity and mechanical ventilation are risk factors for muscle wasting, which predisposes ICU patients to both short-term complications and long-term disabilities resulting from muscle weakness. Unfortunately, the current research does not provide a detailed understanding of the cellular etiology of ICU-acquired weakness, and no standard treatment exists. Therefore, improving knowledge of the mechanisms promoting muscle atrophy in critically ill patients is essential to developing therapeutic strategies to protect against ICU-induced skeletal muscle wasting. To advance our understanding of the mechanism(s) responsible for ICU-acquired weakness, we tested the hypothesis that ICU-induced muscle inactivity promotes a rapid decrease in anabolic signaling/protein synthesis and accelerates proteolysis in both limb and respiratory muscles. To investigate ICU-induced changes in skeletal muscle proteostasis, adult Sprague Dawley rats were anesthetized and mechanically ventilated for 12 h to simulate ICU care. Measurements of anabolic signaling, protein synthesis, and proteolytic activity in the limb muscles (plantaris and soleus) and respiratory muscles (parasternal and intercostal) revealed ICU-induced reductions in both anabolic signaling (i.e., AKT/mTOR pathway) and muscle protein synthesis. Moreover, simulated ICU care resulted in increased biomarkers of accelerated proteolysis in both limb and respiratory muscles. These novel findings reveal that disturbances in limb and respiratory muscle proteostasis occur rapidly during ICU-induced muscle inactivity, irrespective of the muscle function or muscle fiber type.
登录
查看更多内容
影响因子：
5.7
作者：
Tang, Huibin;Smith, Ira J.;Shrager, Joseph B.
通讯作者：
Shrager, Joseph B.
影响因子：
2
作者：
Rodriguez B;Larsson L;Z'Graggen WJ
通讯作者：
Z'Graggen WJ
影响因子：
120.7
作者：
Puthucheary, Zudin A.;Rawal, Jaikitry;Montgomery, Hugh E.
通讯作者：
Montgomery, Hugh E.
DOI：
10.1164/rccm.200202-088oc
发表时间：
2002-11-15
影响因子：
24.7
作者：
Shanely, RA;Zergeroglu, MA;Powers, SK
通讯作者：
Powers, SK
影响因子：
3.2
作者：
Staron, RS;Hagerman, FC;Toma, K
通讯作者：
Toma, K