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中华重症医学电子杂志 ›› 2017, Vol. 03 ›› Issue (03) : 231 -237. doi: 10.3877/cma.j.issn.2096-1537.2017.03.015

所属专题: 文献

综述

"铁死亡"在横纹肌溶解导致急性肾损伤中的研究现状
吴明1, 苏磊2,()   
  1. 1. 518035 深圳市第二人民医院重症医学科
    2. 508010 广州军区广州总医院重症医学科
  • 收稿日期:2016-12-28 出版日期:2017-08-28
  • 通信作者: 苏磊
  • 基金资助:
    国家自然科学基金(81671896); 广东省医学科学技术研究基金(A2016353); 广东省深圳市科技创新委项目(JCY20150330102401099、JCYJ20160425103130218)

Current research situation of ferroptosis in rhabdomyolysis-induced acute kidney injury

Ming Wu1, Lei Su2,()   

  1. 1. Department of Critical Care Medicine of The Second People′s Hospital of ShenZhen, Shenzhen 518035, China
  • Received:2016-12-28 Published:2017-08-28
  • Corresponding author: Lei Su
  • About author:
    Corresponding author: Su Lei, Email:
引用本文:

吴明, 苏磊. "铁死亡"在横纹肌溶解导致急性肾损伤中的研究现状[J/OL]. 中华重症医学电子杂志, 2017, 03(03): 231-237.

Ming Wu, Lei Su. Current research situation of ferroptosis in rhabdomyolysis-induced acute kidney injury[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(03): 231-237.

肌肉的直接创伤,剧烈运动及肌肉代谢改变,化学、物理或生物制剂的毒性作用以及遗传等因素均可导致横纹肌溶解(RM)。以往发现大量肌红蛋白引起肾小管堵塞、肾血管收缩、触发剧烈炎症反应、诱导细胞凋亡是横纹肌溶解致肾损伤的主要机制。肌红蛋白介导肾小管上皮细胞发生脂质过氧化与谷氨酸代谢密切相关,通过多种信号分子介导近端肾小管铁死亡(ferroptosis),铁死亡是肌红蛋白诱导急性肾损伤(AKI)更为重要的机制。铁螯合剂,即去铁胺可减轻横纹肌溶解诱导的急性肾损伤,因其水溶性强,具有一定的肾毒性,限制了其在临床上的应用。去铁胺通过结合铁金刚烷衍生物,增加脂溶性,减少细胞毒性及保留抗炎和抗氧化能力。来自植物木蝴蝶等的黄芩素,具有抗细胞铁死亡能力,可能作为铁死亡相关组织损伤的治疗。高分子截留血液滤过(HCO)可以清除肌红蛋白,已成为横纹肌溶解导致急性肾损伤肾替代治疗优先选择的模式。

Rhabdomyolysis (RM) can be induced by severe muscles injury, strenuous exercise, intrinsic metabolic of muscle cells, and the toxic effects of chemical, physical, or biological agents. Myoglobin induced tubular obstruction, renal vasoconstriction, inflammation and apoptosis play a key role in rhabdomyolysis-associated kidney damage. Lipid peroxidation of renal tubular epithelial cells mediated by myoglobin is closely related to glutamate metabolism, whichinduce renal proximal tubular ferroptosis through a variety of signal molecules. Ferroptosis plays a key role in myoglobin induced acute renal injury (AKI). Desferrioxamine is an iron chelator that inhibits lipid peroxidation by reducing myoglobin-derived acute kidney injury. However, it is limited in clinical practice because of its hydrophilic properties and direct nephrotoxic effects.. Deferoxamine conjugated to adamantyl derivatives, which obtains lipophilic capacity. Baicalein, a kind of traditional Chinese medicine, can enhance cellular anti-ferroptosis capacity, which may be a potential therapeutic agent for ferroptosis-associated tissue injury. Myoglobin can be removed by high cut off hemofiltration (HCO), which has become the preferred treatment mode of renal replacement of RM-induced AKI.

图1 横纹肌溶解的分子机制图
图2 肌红蛋白诱导急性肾衰的机制
图3 铁代谢与铁死亡模式图
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