Study on the protective mechanism of Ferrostatin-1 against sepsis-associated acute kidney injury in mice

JIA Meng; ZHENG Jun; LIU Bin; HAN Jin-yu

doi:10.11659/jjssx.09E025098

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Study on the protective mechanism of Ferrostatin-1 against sepsis-associated acute kidney injury in mice

Basic Research | 更新时间：2026-07-24

- Study on the protective mechanism of Ferrostatin-1 against sepsis-associated acute kidney injury in mice
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 7, Pages: 597-601(2026)
- 作者机构：
  
  新疆医科大学第六附属医院重症医学科，新疆乌鲁木齐 830002
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.09E025098
  CLC： R692.9
- Received：24 September 2025，
  
  Online First：24 July 2026，
  
  Published：25 July 2026
- 稿件说明：
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贾萌,郑军,刘斌等.Ferrostatin-1对小鼠脓毒症相关急性肾损伤的保护机制研究[J].局解手术学杂志,2026,35(07):597-601.

JIA Meng,ZHENG Jun,LIU Bin,et al.Study on the protective mechanism of Ferrostatin-1 against sepsis-associated acute kidney injury in mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(07):597-601.
贾萌,郑军,刘斌等.Ferrostatin-1对小鼠脓毒症相关急性肾损伤的保护机制研究[J].局解手术学杂志,2026,35(07):597-601. DOI： 10.11659/jjssx.09E025098.

JIA Meng,ZHENG Jun,LIU Bin,et al.Study on the protective mechanism of Ferrostatin-1 against sepsis-associated acute kidney injury in mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(07):597-601. DOI： 10.11659/jjssx.09E025098.

摘要

目的

探讨铁死亡抑制剂铁抑素-1（Ferrostatin-1）对脓毒症相关急性肾损伤（SA-AKI）的保护效应及其潜在机制。

方法

24只6~8周龄C57BL/6雄性小鼠随机分为NC组、Sham组、Model组和Model+Ferrostatin-1组，每组6只。建立SA-AKI小鼠模型，检测各组小鼠肾功能指标[尿素氮（BUN）、肌酐（Cr）、中性粒细胞明胶酶相关脂钙蛋白（NGAL）]、活性氧（ROS）水平、铁死亡相关指标[Fe²⁺、丙二醛（MDA）、谷胱甘肽（GSH）]及炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）]水平。Western blot检测肾组织中Ferrostatin-1和SLC39A14的蛋白表达。在人肾近端小管上皮细胞实验中，通过敲低Ferrostatin-1观察其对细胞中SLC39A14表达的影响。利用腺病毒颗粒介导的过表达SLC39A14技术，验证其在Ferrostatin-1调控HK-2细胞中ROS水平中的作用。

结果

与Sham组相比，Model组小鼠肾组织中Ferrostatin-1表达水平降低（

0.05），SLC39A14表达水平升高（

0.01）。与Model组相比，Model+Ferrostatin-1组小鼠肾组织中BUN、Cr、NGAL、ROS、Fe

、MDA、TNF-α、IL-1β和IL-6水平均降低（

0.05），GSH水平升高（

0.05）。体外HK-2细胞实验表明，敲低细胞中的Ferrostatin-1可上调SLC39A14的表达（

0.001）。而过表达SLC39A14则逆转了Ferrostatin-1对脂多糖诱导的HK-2细胞ROS升高的抑制作用（

0.05）。

结论

Ferrostatin-1可通过抑制铁死亡、减轻氧化应激和炎症反应，对SA-AKI发挥保护作用，其机制可能与负向调控SLC39A14的表达有关。

Abstract

Objective

To investigate the protective effect of ferroptosis inhibitor Ferrostatin-1 against sepsis-associated acute kidney injury （SA-AKI） and its possible mechanisms.

Methods

Twenty-four male C57BL/6 mice aged 6 to 8 weeks were randomly divided into four groups with 6 mice in each group： NC group， Sham group， Model group and Model+Ferrostatin-1 group. A mouse model of SA-AKI was established. Renal function indicators ［blood urea nitrogen （BUN）， creatinine （Cr） and neutrophil gelatinase-associated lipocalin （NGAL）］， renal tissue reactive oxygen species （ROS） level， ferroptosis-related indexes ［Fe²⁺， malondialdehyde （MDA）， and glutathione （GSH）］ as well as inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）］ in mice of each group were detected.Western blot was adopted to detect the protein expression of Ferrostatin-1 and SLC39A14 in renal tissues.In experiments on human renal proximal tubular epithelial cells， the effect of Ferrostatin-1 knockdown on the expression of SLC39A14 in cells was investigated. Adenovirus particle-mediated overexpression of SLC39A14 was applied to verify its role in Ferrostatin-1-regulated intracellular ROS levels in HK-2 cells.

Results

Compared with the Sham group， the expression of Ferrostatin-1 was significantly decreased （

0.05）， while the expression of SLC39A14 was markedly increased （

0.01） in renal tissues of the Model group. Compared with the Model group， the levels of BUN， Cr， NGAL， ROS， Fe²⁺， MDA， TNF-α， IL-1β and IL-6 were significantly reduced （

0.05）， whereas GSH level was increased （

0.05） in the Model+Ferrostatin-1 group. In vitro experiments on HK-2 cells showed that knockdown of Ferrostatin-1 in cells upregulated the expression of SLC39A14 （

0.001）. Conversely， over-expression of SLC39A14 reversed the inhibitory effects of Ferrostatin-1 on lipopolysaccharide-induced ROS increase in HK-2 cells （

0.05）.

Conclusion

Ferrostatin-1 exerts protective effects against SA-AKI via inhibiting ferroptosis， alleviating oxidative stress and inflammatory response， and its possible mechanism may involve the negative regulation of SLC39A14 expression.

关键词

Keywords

references

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