Sepsis-induced myopathy.
Sepsis-induced myopathy.
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DOI：
10.1097/ccm.0b013e3181b6e439
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发表时间：
2009-10
影响因子：
8.8
通讯作者：
Supinski GS
中科院分区：
文献类型：
--
作者：
Callahan LA;Supinski GS
脓毒症是危重患者发病率和死亡率的主要原因，尽管在治疗方面取得了进展，但死亡率仍然很高。在幸存者中，败血症增加了患持续性获得性虚弱综合征的风险，这些综合征同时影响呼吸肌和四肢肌肉。这种后天的虚弱会导致机械通气持续时间延长、脱机困难、功能受损、运动受限，以及与健康相关的生活质量下降。大量证据表明，脓毒症会导致一种肌病，其特征是肌肉力量生成能力降低、萎缩(肌肉质量丧失)和生物能量改变。脓毒症引起与兴奋收缩偶联相关的多个亚细胞部位的紊乱，如降低膜兴奋性、损伤肌膜、影响肌浆网改变钙稳态、破坏收缩蛋白相互作用等。肌肉萎缩发生的时间较晚，是蛋白质降解增加和蛋白质合成减少的结果。此外，脓毒症会导致肌肉线粒体功能的显著异常，当严重时，这些变化与死亡增加相关。脓毒症引起骨骼肌改变的机制与促炎症细胞因子的过度局部化、自由基生成的显著增加以及蛋白酶体上游的蛋白分解途径(包括caspase和calain)的激活有关。新的数据表明，靶向抑制这些通路可能改变脓毒症诱导的肌病的演变和进展，并潜在地减少脓毒症介导的获得性虚弱综合征的发生。
Sepsis is a major cause of morbidity and mortality in critically ill patients, and despite advances in management, mortality remains high. In survivors, sepsis increases the risk for the development of persistent acquired weakness syndromes affecting both the respiratory muscles and the limb muscles. This acquired weakness results in prolonged duration of mechanical ventilation, difficulty weaning, functional impairment, exercise limitation, and poor health-related quality of life. Abundant evidence indicates that sepsis induces a myopathy characterized by reductions in muscle force-generating capacity, atrophy (loss of muscle mass), and altered bioenergetics. Sepsis elicits derangements at multiple subcellular sites involved in excitation contraction coupling, such as decreasing membrane excitability, injuring sarcolemmal membranes, altering calcium homeostasis due to effects on the sarcoplasmic reticulum, and disrupting contractile protein interactions. Muscle wasting occurs later and results from increased proteolytic degradation as well as decreased protein synthesis. In addition, sepsis produces marked abnormalities in muscle mitochondrial functional capacity and when severe, these alterations correlate with increased death. The mechanisms leading to sepsis-induced changes in skeletal muscle are linked to excessive localized elaboration of proinflammatory cytokines, marked increases in free-radical generation, and activation of proteolytic pathways that are upstream of the proteasome including caspase and calpain. Emerging data suggest that targeted inhibition of these pathways may alter the evolution and progression of sepsis-induced myopathy and potentially reduce the occurrence of sepsis-mediated acquired weakness syndromes.