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石榴提取物通过抑制 NF-κB 通路改善大鼠肾缺血/再灌注损伤。

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway.

机构信息

Faculty of Pharmacy, Department of Pharmacology and Toxicology, 158395Mansoura University, Mansoura, Egypt.

Nephrology and Urology Center, Faculty of Medicine, 158395Mansoura University, Mansoura, Egypt.

出版信息

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S573-S582. doi: 10.1177/09603271211041998. Epub 2021 Nov 20.

Abstract

Inflammation and oxidative stress are the major pathways involved in ischemia-reperfusion (I/R)-induced renal injury. This study was designed to evaluate the potential effect of pomegranate against I/R-induced renal injury. I/R injury was induced in nephrectomized rats by unilateral occlusion of the left renal pedicle for 45 min followed by 24 h of perfusion. Pomegranate succeeded to decrease serum levels of creatinine, potassium, and urea nitrogen, along with increasing creatinine clearance. Pomegranate also decreased I/R-induced changes in histopathological examination. Pomegranate attenuated the renal inflammatory response reflected by the suppression of nuclear factor κB p65 DNA binding activity, the upregulation of inhibitory protein kappa B-alpha mRNA expression, the downregulation of mRNA and protein expression of tumor necrosis factor α, in addition to the reduced myeloperoxidase activity and mRNA expression. Additionally, pomegranate attenuated oxidative stress likely through the modulation of lipid peroxidation and antioxidant levels reflected by the decreased MDA content and the increased glutathione level and superoxide dismutase activity. Results confirm the potential protective effect of pomegranate against I/R-induced renal injury through its anti-inflammatory and anti-oxidant effects mediated through the upregulation of inhibitory protein kappa B-alpha, the inhibition of NF-κB activity, and the associated TNF-α release, neutrophil infiltration, and oxidative stress.

摘要

炎症和氧化应激是缺血再灌注(I/R)诱导的肾损伤的主要途径。本研究旨在评估石榴对 I/R 诱导的肾损伤的潜在作用。通过单侧阻断左肾蒂 45 分钟,然后灌注 24 小时,在肾切除大鼠中诱导 I/R 损伤。石榴成功降低了血清肌酐、钾和尿素氮的水平,同时增加了肌酐清除率。石榴还减轻了 I/R 引起的组织病理学检查变化。石榴通过抑制核因子 κB p65 DNA 结合活性、上调抑制蛋白 kappa B-α mRNA 表达、下调肿瘤坏死因子 α 的 mRNA 和蛋白表达,以及降低髓过氧化物酶活性和 mRNA 表达,减轻了肾的炎症反应。此外,石榴通过调节脂质过氧化和抗氧化水平,减轻氧化应激,表现为 MDA 含量降低,谷胱甘肽水平升高,超氧化物歧化酶活性增强。结果证实,石榴通过上调抑制蛋白 kappa B-α、抑制 NF-κB 活性以及相关的 TNF-α 释放、中性粒细胞浸润和氧化应激,对 I/R 诱导的肾损伤具有潜在的保护作用。

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