Nephron. 2018;139(4):342-348. doi: 10.1159/000489940. Epub 2018 May 31.
BACKGROUND/AIMS: Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown.
A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: "acute kidney injury," "necrosis," "necroptosis," "necroinflammation."
The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed.
There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern.
背景/目的：程序性细胞坏死是一个不断发展的研究领域，对急性肾损伤（AKI）具有重要意义。本文重点综述了 AKI 中程序性细胞坏死（细胞坏死的一种形式）的研究进展，明确了目前已知和未知的内容。
我们在 PUBMED 和 ScienceDirect 数据库中检索了 1957 年 1 月至 2018 年 4 月期间的相关文献，检索词包括“acute kidney injury”“necrosis”“necroptosis”“necroinflammation”。
程序性细胞坏死信号通路涉及多种蛋白，包括受体相互作用蛋白 1（RIPK1）、RIPK3 和混合谱系激酶结构域样蛋白（MLKL）以及 MLKL 调节蛋白 RGMb。我们对这些蛋白的基因敲除小鼠、或多或少具有特异性的抑制性化合物以及各种 AKI 动物模型的实验证据进行了综述。
大量研究表明程序性细胞坏死在 AKI 中发挥作用，但也有一些研究报告了不一致的证据，这可能与具体的模型和分析时间点有关。Mlkl 敲除小鼠是目前研究体内程序性细胞坏死的最特异、可靠的实验工具（在肾脏病中）。需要进一步评估 AKI 中抑制程序性细胞坏死的临床潜力，但 AKI 定义和复杂临床情况下的概念问题仍然值得关注。
