Acute rhabdomyolysis and inflammation
Acute rhabdomyolysis and inflammation
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DOI：
10.1007/s10545-015-9827-7
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发表时间：
2015-07-01
影响因子：
4.2
通讯作者：
de Lonlay, Pascale
中科院分区：
文献类型：
--
作者：
Hamel, Yamina;Mamoune, Asmaa;de Lonlay, Pascale
横纹肌溶解症是由骨骼肌纤维快速分解引起的，导致潜在有毒的细胞内容物渗漏到体循环中。由肌膜直接损伤引起的后天性病因最为常见。遗传原因包括：i) 代谢导致能量产生失败，包括线粒体脂肪酸 β 氧化缺陷、LPIN1 突变、糖原分解和糖酵解的先天性错误、更罕见的线粒体呼吸链缺陷、嘌呤缺陷和过氧化体 α-甲基酰基辅酶 A 消旋酶缺陷 (AMACR)，ii) 肌肉营养不良和肌病的结构性原因，iii) RYR1 基因突变引起的钙泵障碍，iv) 炎症原因肌炎。无论横纹肌溶解症的病因如何，病理学都遵循共同的途径，要么是细胞内钙浓度增加（后天性原因）对肌膜造成直接损伤，要么是能量产生失败（遗传性原因），从而导致纤维坏死。横纹肌溶解症常常由发热性疾病或运动引起。这些病症与两个事件有关，即体温升高和促炎介质（例如细胞因子和趋化因子）的高循环水平。为了在能量代谢、蛋白质热稳定性和精氨酸治疗的潜在益处的背景下说明这些观点，我们重点关注横纹肌溶解症的罕见原因——醛缩酶 A 缺乏。此外，我们对脂质 1 (LPIN1) 缺乏症的研究提出了一种可能性，即与横纹肌溶解有关的几种疾病与促炎细胞因子有关，甚至可能主要代表促炎性疾病。因此，不仅对肌肉功能至关重要的突变蛋白的热稳定性，而且促炎细胞因子本身也可能导致代谢失代偿和横纹肌溶解。
Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular content into the systemic circulation. Acquired causes by direct injury to the sarcolemma are most frequent. The inherited causes are: i) metabolic with failure of energy production, including mitochondrial fatty acid beta-oxidation defects, LPIN1 mutations, inborn errors of glycogenolysis and glycolysis, more rarely mitochondrial respiratory chain deficiency, purine defects and peroxysomal alpha-methyl-acyl-CoA-racemase defect (AMACR), ii) structural causes with muscle dystrophies and myopathies, iii) calcium pump disorder with RYR1 gene mutations, iv) inflammatory causes with myositis. Irrespective of the cause of rhabdomyolysis, the pathology follows a common pathway, either by the direct injury to sarcolemma by increased intracellular calcium concentration (acquired causes) or by the failure of energy production (inherited causes), which leads to fiber necrosis. Rhabdomyolysis are frequently precipitated by febrile illness or exercise. These conditions are associated with two events, elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines. To illustrate these points in the context of energy metabolism, protein thermolability and the potential benefits of arginine therapy, we focus on a rare cause of rhabdomyolysis, aldolase A deficiency. In addition, our studies on lipin-1 (LPIN1) deficiency raise the possibility that several diseases involved in rhabdomyolysis implicate pro-inflammatory cytokines and may even represent primarily pro-inflammatory diseases. Thus, not only thermolability of mutant proteins critical for muscle function, but also pro-inflammatory cytokines per se, may lead to metabolic decompensation and rhabdomyolysis.