Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
Physiol Genomics. 2012 Sep 18;44(18):865-77. doi: 10.1152/physiolgenomics.00031.2012. Epub 2012 Jul 31.
Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover, the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin-induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis, for 5 days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of > 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity, and transcriptional regulation. Genes involved in the regulation of the oxidative stress response and cytoskeletal/sarcomeric and heat shock proteins were on the other hand downregulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients, and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.
严重的肌肉消耗和肌肉功能丧失会对接受机械通气的重症监护病房（ICU）患者的康复产生重大负面影响，这些影响会持续很长时间，甚至在他们出院后仍然存在；此外，其潜在机制尚不清楚。机械通气（MV）和固定引起的改变在这些后果中起着重要作用，包括内毒素引起的败血症。本研究旨在探讨败血症如何加重与呼吸机和固定相关的肢体肌肉功能障碍。因此，研究人员研究了暴露于 ICU 干预（即固定、镇静和 MV）的猪的比目鱼肌基因表达情况，这些干预单独或与败血症联合使用 5 天。在之前的研究中，研究人员已经表明，ICU 干预单独或与败血症联合使用不会影响第 5 天的肌肉纤维大小，但当败血症加入到 ICU 干预中时，单纤维最大力与横截面积的比值（比力）显著下降。根据微阵列数据，败血症的加入 ICU 干预诱导了 >500 个基因的失调，例如，参与趋化因子活性、激酶活性和转录调控的基因的表达增加。而当败血症加入到 ICU 干预中时，与氧化应激反应调节、细胞骨架/肌节和热休克蛋白调节相关的基因则下调。因此，败血症对重症 ICU 患者的肌肉功能有显著的负面影响，趋化因子活性和热休克蛋白基因在这种特定的肌肉消耗状态中发挥着重要作用。
