AIM Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co-inducer BGP-15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP-15 on a limb muscle (soleus muscle) in response to the ICU condition. METHODS Sprague-Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham-operated controls. RESULTS BGP-15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post-translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP-15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP-15 had a strong positive effect on survival compared with untreated animals. CONCLUSIONS BGP-15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long-term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post-translational modifications and the loss of myosin.

中文翻译：

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伴侣伴侣诱导剂BGP-15可减轻大鼠ICU模型中比目鱼肌的早期收缩功能障碍。

AIM重症肌病（CIM）代表了现代重症监护的常见后果，对患者的健康造成负面影响并显着增加了医疗保健成本；但是，除了对症和支持性干预措施外，没有其他可用的治疗方法。伴侣伴侣诱导剂BGP-15先前已显示对重症监护病房（ICU）病情暴露的大鼠rats肌有积极作用。在这项研究中，我们旨在探讨BGP-15对ICU条件下肢体肌肉（比目鱼肌）的影响。方法将Sprague-Dawley大鼠置于ICU条件下5、8和10天，并与未经治疗的假手术对照组进行比较。结果暴露于ICU条件下5天后，BGP-15显着改善了比目鱼肌纤维的力量。这种改善与保护肌球蛋白免受翻译后肌球蛋白的修饰，线粒体结构/生物发生的改善以及MuRF1和Fbxo31 E3连接酶的表达降低有关。在较长的持续时间（8天和10天）中，当CIM的特征变得明显时，即肌球蛋白的优先丢失，BGP-15没有保护作用。与对骨骼肌的影响无关，与未经治疗的动物相比，BGP-15对存活具有很强的积极作用。结论BGP-15治疗改善了比目鱼肌纤维和运动蛋白的功能，暴露于ICU条件后5天，但并没有在较长时间（8天和10天）出现肌球蛋白的优先损失时改善。因此，