Nutrim School for Nutrition, Toxicology and Metabolism, Department of Anatomy and Embryology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):548-53. doi: 10.1097/MCO.0b013e32834b6e79.
Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments.
In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism.
Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity.
肌肉减少和肌肉氧化代谢受损是慢性呼吸衰竭（CRF）的常见肺外特征，这显著增加了疾病负担。本综述旨在探讨一个问题，即这种疾病的明显后果——缺氧是否实际上在这些肌肉损伤中起因果作用。
在实验模型中，缺氧在肌肉萎缩和代谢损伤中的因果作用已被明确证实。尽管缺氧诱导因子和核因子 kappa B 是这些缺氧诱导变化的潜在介质，但它们的真正参与仍有待证实。在患有 CRF 的患者的肌肉中也观察到了这些实验模型中肌肉质量和氧化代谢调节中断的分子特征，这表明缺氧的因果作用，但尚无定论。已经证明，包括但不限于旨在缓解缺氧的治疗方法，可以部分但不能完全恢复 CRF 患者的肌肉质量和氧化能力，这可能意味着营养调节底物代谢的附加效应。
虽然缺氧显然会影响骨骼肌的维持，但仍需证实缺氧是否以及通过哪些潜在的分子机制在 CRF 相关的肌肉萎缩和氧化能力受损中起因果作用。
