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Sirt1/Nrf2/TNFα; TLR4/Myd88/NF-κB 信号通路参与介导盐酸安非他酮在心肌梗死大鼠模型中的肝保护作用。

Sirt1/Nrf2/TNFα; TLR4/Myd88/NF-κB signaling pathways are involved in mediating hepatoprotective effect of bupropion in rat model of myocardial infarction.

机构信息

Department of Medical Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.

Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudia Arabia.

出版信息

Immunopharmacol Immunotoxicol. 2024 Dec;46(6):872-883. doi: 10.1080/08923973.2024.2415461. Epub 2024 Oct 16.

Abstract

BACKGROUND

The aim of the current study is to identify the possible protective effect of bupropion (BUP) on liver injury in rat model of myocardial infarction (MI). BUP was administered in the presence and absence of MI.

MATERIALS AND METHODS

Thirty-two Wistar adult male rats were randomly arranged into four groups: control, BUP (30 mg/kg/day, intraperitoneal) for 28 days, isoproterenol (ISO) was injected subcutaneous (85 mg/kg) in the 26th and 27th days and BUP/ISO groups. Cardiac and hepatic enzymes were measured, also Hepatic oxidative stress indicators, as well as inflammatory and apoptotic biomarkers, were evaluated. Cardiac and hepatic histopathological examination and hepatic nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) immunohistochemical study were also detected.

RESULTS

ISO significantly increased cardiac and hepatic enzymes, hepatic oxidative stress, inflammatory, apoptotic, with a histopathological picture of cardiac and hepatic damage and high hepatic NF-κB immunoexpression were detected. BUP significantly normalized the upraised oxidative, inflammatory, and apoptotic parameters, with an impressive improvement in the histopathological picture and a reduction in hepatic NF-κB immunoexpression.

CONCLUSION

BUP protects against liver injury on top of MI in rat model modulation of Sirtuin type 1 (Sirt1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tumor necrosis factor α (TNFα); Toll-like receptor 4 (TLR4)/Hepatic myeloid differentiation primary response 88(Myd88)/NF-κB signaling pathways.

摘要

背景

本研究旨在探讨丁丙诺啡(BUP)对心肌梗死(MI)大鼠模型肝损伤的可能保护作用。BUP 在存在和不存在 MI 的情况下给药。

材料和方法

32 只 Wistar 成年雄性大鼠随机分为四组:对照组、BUP(30mg/kg/天,腹腔内)28 天、26 日和 27 日皮下注射异丙肾上腺素(ISO)(85mg/kg)和 BUP/ISO 组。测量心脏和肝脏酶,评估肝氧化应激指标以及炎症和凋亡生物标志物。还进行了心脏和肝脏组织病理学检查以及核因子 kappa 轻链增强子活化 B 细胞(NF-κB)免疫组织化学研究。

结果

ISO 显著增加了心脏和肝脏酶、肝氧化应激、炎症和凋亡,并检测到心脏和肝脏损伤的组织病理学图像以及高肝 NF-κB 免疫表达。BUP 显著正常化了升高的氧化、炎症和凋亡参数,组织病理学图像显著改善,肝 NF-κB 免疫表达减少。

结论

BUP 对大鼠模型中的心肌梗死(MI)上的肝损伤具有保护作用,其机制可能与 Sirtuin 类型 1(Sirt1)/核因子(红系衍生 2)样 2(Nrf2)/肿瘤坏死因子 α(TNFα);Toll 样受体 4(TLR4)/肝髓样分化初级反应 88(Myd88)/NF-κB 信号通路的调节有关。

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