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中华卫生应急电子杂志 ›› 2023, Vol. 09 ›› Issue (02) : 107 -110. doi: 10.3877/cma.j.issn.2095-9133.2023.02.009

综述

铁死亡在脓毒症中的"真善美"
马涛, 李志华, 黄玮玮, 王毅, 于湘友()   
  1. 830054 新疆维吾尔自治区乌鲁木齐,新疆医科大学第一附属医院重症医学科
  • 收稿日期:2023-03-13 出版日期:2023-04-18
  • 通信作者: 于湘友
  • 基金资助:
    国家自然科学基金(82160360)

"Truth, goodness and beauty" of ferroptosis in sepsis

Tao Ma, Zhihua Li, Weiwei Huang   

  • Received:2023-03-13 Published:2023-04-18
引用本文:

马涛, 李志华, 黄玮玮, 王毅, 于湘友. 铁死亡在脓毒症中的"真善美"[J]. 中华卫生应急电子杂志, 2023, 09(02): 107-110.

Tao Ma, Zhihua Li, Weiwei Huang. "Truth, goodness and beauty" of ferroptosis in sepsis[J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2023, 09(02): 107-110.

在重症监护病房(intensive care unit,ICU)所有的急危重症中,脓毒症约占11%,而脓毒症中最严重的两个病症分别是感染性休克和多脏器功能障碍综合征(multiple organ dysfunction syndrome,MODS)。近年来脓毒症的发病率还在以8%~11%的速度递增,整体病死率接近30%,是全世界健康损失的主要原因[1]。抗生素使用后形成的多重耐药,使治疗效果进一步变差,形势之紧迫,值得每位医者高度关注[2]。铁死亡是近年来的研究热点,根据以往经验,患者发生脓毒症时肠内外补铁会进一步加重病情,高浓度血清铁是脓毒症患者90 d死亡的独立因素,而使用铁螯合剂、铁蛋白或预先用铁调素处理脓毒症小鼠是可以通过抑制嗜铁细菌、降低血清铁及减轻氧化应激反应来改善存活率,如果将此理论应用到临床,则需要考虑铁死亡的"双刃剑"效应[3],比如铁的螯合剂在抑制炎症的同时亦可诱导贫血、器官功能障碍等问题,所以铁死亡具体的调控时机还需要大量真实世界的数据支持[4]。脓毒症时,炎症因子可使外周血管扩张,血压下降,为保证心脑等重要脏器的有效灌注,胃肠道的血供首先减少,在炎症合并缺血缺氧的状态下,肠道往往是最先受累和最容易受损的器官,考虑到肠道自身就是细菌库,这为后期炎症加速和菌群转移埋下了伏笔[5]。肠道是机体最大的吸收器官,良好的肠道功能决定着疾病的转归和机体的生长发育。临床上,脓毒症患者中肠道功能正常的患者,ICU住院时间明显缩短。生理状态下肠道黏膜层可分流肠壁80%血运,所以脓毒症期间粘膜层遭受的损害最大。肠道菌群属于混合菌群,对于不同菌群引起的炎症,铁死亡现象均会出现,铁死亡抑制剂可降低革兰氏阳性菌和革兰氏阴性菌引起的白细胞活化[6]。既往研究表明[7],ICU脓毒症患者的病死率和MODS发生率与入院时铁蛋白浓度和血清铁水平成正相关。笔者对脓毒症背景下铁死亡的发生机制及肠道铁死亡现有成果进行概述。

图1 铁死亡的通路图注:TF为转铁蛋白,FPN为铁泵蛋白,Fenton反应为芬顿反应,DFO为去铁胺,ROS为活性氧簇,PUFA为多不饱和脂肪酸,Lipid ROS为脂质过氧化,Ferroptosis为铁死亡,Nrf2为核转录因子红细胞2相关因子2,Glutamate为谷氨酸,Cystine为胱氨酸,GSH为谷胱甘肽,GPX4为谷胱甘肽过氧化物酶4,GSSG为氧化型谷胱甘肽,Erastin为铁死亡诱导剂,System XC-为谷氨酸-胱氨酸反向转运体,GPX4抑制剂为RSL3、Altretamine、DPI17、FIN56、FINO2
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