The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery
The protective role of macrophage migration inhibitory factor in acute kidney injury after cardiac surgery
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DOI：
10.1126/scitranslmed.aan4886
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发表时间：
2018-05-16
影响因子：
17.1
通讯作者：
Boor, Peter
中科院分区：
文献类型：
--
作者：
Stoppe, Christian;Averdunk, Luisa;Boor, Peter
急性肾损伤（阿基）是心脏手术后最常见的并发症。巨噬细胞移动抑制因子（macrophage migration inhibitory factor，MIF）是一种应激调节因子，可保护心肌免受缺血再灌注损伤，但其在阿基发病机制中的作用尚不清楚。在一项观察性研究中，对60例择期常规心脏手术并使用心肺转流术的患者的血清和尿液MIF进行了定量。心脏手术引起MIF血清浓度升高，术后12小时循环MIF高（>中位数）的患者发生阿基的风险显著降低（相对风险降低，72.7%; 95%置信区间，12 - 91.5%; P = 0.03）。在野生型和Mir（-/-）小鼠中，通过30分钟的缺血随后6或24小时的再灌注或通过横纹肌溶解诱导实验性阿基。mf缺陷小鼠表现出肾小管细胞损伤增加，调节性细胞死亡（坏死性凋亡和铁凋亡）增加，氧化应激增强。小鼠缺血再灌注后给予重组MIF治疗可改善阿基。在体外治疗的肾小管上皮细胞与重组MIF减少细胞死亡和氧化应激的谷胱甘肽和硫代巴比妥酸反应物质在缺氧的设置测量。我们的数据提供的证据表明，在实验性缺血-再灌注损伤中，MIF通过保护肾小管上皮细胞发挥肾脏保护作用，这与我们的观察结果一致，即心脏手术患者中高MIF与阿基发生率降低相关。
Acute kidney injury (AKI) represents the most frequent complication after cardiac surgery. Macrophage migration inhibitory factor (MIF) is a stress-regulating cytokine that was shown to protect the heart from myocardial ischemiareperfusion injury, but its role in the pathogenesis of AKI remains unknown. In an observational study, serum and urinary MIF was quantified in 60 patients scheduled for elective conventional cardiac surgery with the use of cardiopulmonary bypass. Cardiac surgery triggered an increase in MIF serum concentrations, and patients with high circulating MIF (>median) 12 hours after surgery had a significantly reduced risk of developing AKI (relative risk reduction, 72.7%; 95% confidence interval, 12 to 91.5%; P = 0.03). Experimental AKI was induced in wild-type and Mir(-/-) mice by 30 min of ischemia followed by 6 or 24 hours of reperfusion, or by rhabdomyolysis. Mf-deficient mice exhibited increased tubular cell injury, increased regulated cell death (necroptosis and ferroptosis), and enhanced oxidative stress. Therapeutic administration of recombinant MIF after ischemia-reperfusion in mice ameliorated AKI. In vitro treatment of tubular epithelial cells with recombinant MIF reduced cell death and oxidative stress as measured by glutathione and thiobarbituric acid reactive substances in the setting of hypoxia. Our data provide evidence of a renoprotective role of MIF in experimental ischemia-reperfusion injury by protecting renal tubular epithelial cells, consistent with our observation that high MIF in cardiac surgery patients is associated with a reduced incidence of AKI.