生物钱币素 A 介导的抗铁细胞生成与减轻脓毒性肾损伤有关

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2024-10-11 DOI:10.1016/j.lfs.2024.123124

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引用次数: 0

摘要

主要方法雄性 BALB/C 小鼠（每组 7 只）在有或没有 LPS（10 毫克/千克，静注）的情况下注射生物茶碱 A（40 毫克/千克，静注）或铁前列素-1（5 毫克/千克，静注）。在长达两周的时间里，每天监测两次存活率。通过H&E染色和分析血清中的血尿素氮（BUN）和肌酐（CR）水平，分别评估肾组织的形态和功能变化。通过 TUNEL 染色、普鲁士蓝染色、铁定量、过氧化脂质定量和谷胱甘肽定量分析肾上皮细胞的死亡。通过对小鼠胚胎成纤维细胞进行 RNA 测序，分析了生物黄芩素 A 的抗败血病机制。主要发现生物黄芩素 A 提高了败血病小鼠的存活率，并抑制了败血病中重要的炎症介质高迁移率基团框 1 的分泌。生物黄酮素 A 能抑制肾小管扩张和肾小管上皮细胞死亡，从而抑制 LPS 引起的肾损伤。此外，经生物变色素 A 处理的内毒素血症小鼠血清中的 BUN 和 CR 水平降低。生物黄铜素 A 可抑制过氧化铁和过氧化脂质的积累，防止肾组织中谷胱甘肽的耗竭。本研究表明，生物黄铜素 A 是一种有效的铁氧化酶抑制剂，是治疗或预防脓毒症相关疾病（如 SA-AKI）的潜在药物。

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Biochanin A-mediated anti-ferroptosis is associated with reduction of septic kidney injury

Aims

This study aimed to investigate the therapeutic potential of biochanin A in a sepsis associated- acute kidney injury (SA-AKI) mouse model induced by lipopolysaccharide (LPS).

Main methods

Male BALB/C mice (n = 7 per group) were injected with biochanin A (40 mg/kg, i.p.) or ferrostatin-1 (5 mg/kg, i.p.) in the presence or absence of LPS (10 mg/kg, i.p.). Survival rates were monitored twice a day for up to 2 weeks. Morphologic and functional changes in kidney tissue were assessed by H&E staining and by analyzing of levels of blood-urea nitrogen (BUN) and creatinine (CR) in serum, respectively. Kidney epithelial cell death was analyzed by TUNEL staining, Prussian blue staining, iron quantification, lipid peroxide quantification, and glutathione quantification. Anti-ferroptosis mechanism of biochanin A was analyzed by RNA sequencing in mouse embryonic fibroblast cells.

Key findings

Biochanin A increased the survival rate of septic mice and inhibited the secretion of high mobility group box 1, an important inflammatory mediator in sepsis. Biochanin A inhibited LPS-induced kidney damage by suppressing dilatation and kidney tubular epithelial cell death. Furthermore, serum levels of BUN and CR were reduced in biochanin A-treated endotoxemic mice. Biochanin A inhibited the accumulation of iron and lipid peroxide and prevented glutathione depletion in the kidney tissue. Also, nine genes associated with the anti-ferroptosis effects of biochanin A were identified by RNA sequencing analysis.

Significance

The present study suggests that biochanin A is an effective inhibitor of ferroptosis, representing a potential treatment or prophylactic for sepsis-related disorders such as SA-AKI.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.