多不饱和脂质的积累助长了铁变态反应，从而导致小鼠肝切除术后肝功能衰竭。

IF 3.6 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Free Radical Research Pub Date : 2024-11-08 DOI:10.1080/10715762.2024.2423691

Can Huang, Jian Gan, Xiangyue Mo, Qingping Li, Leyi Liao, Biao Wang, Xianqiu Wu, Hanbiao Liang, Chen Xie, Tianzhou Peng, Yang Lei, Baoxiong Zhuang, Minghui Zeng, Yonghong Peng, Yisi Chen, Cuiting Liu, Jie Zhou, Kai Wang, Chuanjiang Li

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引用次数: 0

摘要

背景：肝切除术后肝衰竭（PHLF肝切除术后肝衰竭（PHLF）是肝切除术的一种致命并发症。然而，PHLF 中肝细胞损伤的机制仍不明确：方法：通过延长86%肝切除术（eHx）诱导小鼠发生PHLF。脂质组学用于研究 eHx 诱导的残肝脂质改变。评估了铁蛋白沉积，以筛选eHx诱导的肝细胞损伤。评估了铁前列素-1（Fer-1）对 PHLF 的治疗效果：eHx诱导的肝细胞损伤表现为肝细胞增大和肝细胞死亡，并伴有糖原耗竭和脂质积累。脂质组学显示，eHx诱导了有利于铁变态反应的多不饱和脂质的积累。研究发现，在PHLF的发展过程中，铁突变介导了eHx诱导的残肝肝细胞死亡。Fer-1可减轻eHx诱导的小鼠铁突变肝细胞死亡和PHLF：结论：在 PHLF 的发展过程中，铁变态反应在一定程度上介导了 eHx 诱导的肝细胞损伤。肝细胞中多不饱和脂质的积累可能会促进 eHx 诱导的铁变态反应，而针对脂质过氧化是治疗 PHLF 的一种潜在策略。

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Accumulation of polyunsaturated lipids fuels ferroptosis to promote liver failure after extended hepatectomy in mice.

Background: Post-hepatectomy liver failure (PHLF) is a fatal complication of hepatectomy. However, the mechanism of hepatocyte injury in PHLF remains elusive.

Methods: PHLF was induced by extended 86% hepatectomy (eHx) in mice. Lipidomics was performed to investigate the eHx-induced lipid alteration in the residual liver. Ferroptosis was assessed to screen the hepatocyte injury induced by eHx. The therapeutic effects of ferrostatin-1 (Fer-1) on PHLF were evaluated.

Results: PHLF was induced by eHx with elevation in markers of hepatocyte injury and mortality in mice within 48 h after surgery. eHx-induced hepatocyte injury was manifested by hepatocyte enlargement and hepatocyte death with glycogen depletion and lipid accumulation. Lipidomics revealed that eHx induced the accumulation of ferroptosis-favored polyunsaturated lipids. Ferroptosis was found to mediate the eHx-induced hepatocyte death in the residual liver during the development of PHLF. Fer-1 could attenuate the eHx-induced ferroptotic hepatocyte death and PHLF in mice.

Conclusions: Ferroptosis partly mediates the eHx-induced hepatocyte injury during the development of PHLF. Accumulation of polyunsaturated lipids in hepatocytes may promote eHx-induced ferroptosis, and targeting lipid peroxidation is a potential therapeutic strategy for PHLF.

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来源期刊

Free Radical Research 生物-生化与分子生物学

CiteScore

6.70

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.