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接受阿霉素化疗和槲皮素的大鼠肾脏中中间丝蛋白表达模式及炎症反应变化

Intermediate filament protein expression pattern and inflammatory response changes in kidneys of rats receiving doxorubicin chemotherapy and quercetin.

作者信息

Khalil Samah R, Mohammed Amany Tharwat, Abd El-Fattah Amir H, Zaglool Asmaa W

机构信息

Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.

Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.

出版信息

Toxicol Lett. 2018 May 15;288:89-98. doi: 10.1016/j.toxlet.2018.02.024. Epub 2018 Feb 21.

Abstract

The aim of this study was to explore the potential effects of quercetin (QUR) on doxorubicin (DOX)-induced nephrotoxicity. Fifty male rats were assigned to five groups (10 rats each): a control group, a DOX-treated group (total dose, 15 mg/kg bw, intraperitoneally), a QUR-treated group (50 mg/kg bw/day, orally), a prophylaxis co-treated group, and a therapeutic co-treated group. Biochemical parameters and renal function were measured. Moreover, kidney tissues were homogenized for inflammatory marker evaluation and real-time qPCR analysis to determine the changes in intermediate filament protein mRNA levels (desmin, vimentin, connexin 43 and nestin). QUR exhibited a significant nephroprotective effect, particularly when it was administered prior to and simultaneously with DOX treatment (prophylaxis co-treated group). This role was biochemically demonstrated by the significant modulation of DOX-induced body weight loss, hypoproteinemia, and elevated serum creatinine and urea. Moreover, QUR attenuated the inflammatory response as shown by decreased renal nitric oxide, tumor necrosis factor-α production and myeloperoxidase activity elicited by DOX injection. These biochemical improvements were accompanied by a significant histopathological restoration of rat kidney tissue and successful down-regulation of the intermediate filament protein mRNA levels, indicating amelioration of DOX-induced podocyte injury. Taken together, these results conclusively demonstrated that QUR administration has a prophylactic effect on DOX-induced injury in the rat kidney.

摘要

本研究的目的是探讨槲皮素(QUR)对阿霉素(DOX)诱导的肾毒性的潜在影响。将50只雄性大鼠分为五组(每组10只):对照组、DOX处理组(总剂量15mg/kg体重,腹腔注射)、QUR处理组(50mg/kg体重/天,口服)、预防联合处理组和治疗联合处理组。检测生化参数和肾功能。此外,将肾组织匀浆以评估炎症标志物并进行实时定量PCR分析,以确定中间丝蛋白mRNA水平(结蛋白、波形蛋白、连接蛋白43和巢蛋白)的变化。QUR表现出显著的肾保护作用,尤其是在DOX治疗前和治疗期间同时给药时(预防联合处理组)。DOX诱导的体重减轻、低蛋白血症以及血清肌酐和尿素升高得到显著调节,从生化角度证明了这一作用。此外,QUR减轻了炎症反应,表现为DOX注射引起的肾一氧化氮、肿瘤坏死因子-α生成和髓过氧化物酶活性降低。这些生化改善伴随着大鼠肾组织显著的组织病理学恢复以及中间丝蛋白mRNA水平的成功下调,表明DOX诱导的足细胞损伤得到改善。综上所述,这些结果确凿地证明了给予QUR对DOX诱导的大鼠肾损伤具有预防作用。

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