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香叶木素通过抑制SIRT1/GPX4介导的铁死亡减轻金黄色葡萄球菌诱导的乳腺炎。

Diosmetin alleviates S. aureus-induced mastitis by inhibiting SIRT1/GPX4 mediated ferroptosis.

作者信息

Zhao Lihua, Jin Lei, Yang Bin

机构信息

Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.

Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.

出版信息

Life Sci. 2023 Oct 15;331:122060. doi: 10.1016/j.lfs.2023.122060. Epub 2023 Aug 29.

DOI:10.1016/j.lfs.2023.122060
PMID:37652155
Abstract

AIMS

Microbial infection is the main factor that induces mastitis. Staphylococcus aureus (S. aureus) is a major pathogen associated with mastitis. The purpose of this study was to investigate the effects of diosmetin on S. aureus-induced mastitis.

MATERIALS AND METHODS

The mice were divided into six groups: control group, S. aureus group, diosmetin (12.5, 25, 50 mg/kg) + S. aureus groups, and diosmetin (50 mg/kg) + S. aureus + EX-527 (10 mg/kg) group. S. aureus was injected into the mammary gland to establish a mouse mastitis model. Diosmetin was administered 1 h before S. aureus treatment.

KEY FINDINGS

Our results showed that diosmetin significantly alleviated the pathological changes of mammary gland induced by S. aureus. Diosmetin alleviated myeloperoxidase (MPO) activity, and the release of TNF-α and IL-1β, and nuclear factor kappa-B (NF-κB) activation. Moreover, diosmetin inhibited malondialdehyde (MDA) and Fe levels induced by S. aureus. Diosmetin upregulated ATP, glutathione (GSH) production and glutathione peroxidase 4 (GPX4) expression, which were decreased by S. aureus. Furthermore, the expression of Sirtuin 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) was upregulated by diosmetin. In addition, the inhibitory effects of diosmetin on S. aureus-induced inflammation and ferroptosis were prevented by the SIRT1 inhibitor EX-527.

SIGNIFICANCE

In conclusion, the data indicated that diosmetin suppressed S. aureus-induced mastitis by attenuating inflammation and ferroptosis.

摘要

目的

微生物感染是诱发乳腺炎的主要因素。金黄色葡萄球菌是与乳腺炎相关的主要病原体。本研究旨在探讨香叶木素对金黄色葡萄球菌诱导的乳腺炎的影响。

材料与方法

将小鼠分为六组:对照组、金黄色葡萄球菌组、香叶木素(12.5、25、50mg/kg)+金黄色葡萄球菌组以及香叶木素(50mg/kg)+金黄色葡萄球菌+EX-527(10mg/kg)组。将金黄色葡萄球菌注入乳腺以建立小鼠乳腺炎模型。在金黄色葡萄球菌处理前1小时给予香叶木素。

主要发现

我们的结果表明,香叶木素显著减轻了金黄色葡萄球菌诱导的乳腺病理变化。香叶木素减轻了髓过氧化物酶(MPO)活性、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的释放以及核因子κB(NF-κB)的激活。此外,香叶木素抑制了金黄色葡萄球菌诱导的丙二醛(MDA)和铁水平。香叶木素上调了因金黄色葡萄球菌而降低的三磷酸腺苷(ATP)、谷胱甘肽(GSH)生成以及谷胱甘肽过氧化物酶4(GPX4)的表达。此外,香叶木素上调了沉默调节蛋白1(SIRT1)、核因子红细胞2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达。此外,SIRT1抑制剂EX-527阻止了香叶木素对金黄色葡萄球菌诱导的炎症和铁死亡的抑制作用。

意义

总之,数据表明香叶木素通过减轻炎症和铁死亡来抑制金黄色葡萄球菌诱导的乳腺炎。

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