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先前运动对顺铂诱导的大鼠肾损伤的影响。

Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats.

作者信息

Francescato Heloísa D C, Almeida Lucas F, Reis Natany G, Faleiros Camila M, Papoti Marcelo, Costa Roberto S, Coimbra Terezila M

机构信息

Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

School of Physical Education and Sports of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

出版信息

Kidney Blood Press Res. 2018;43(2):582-593. doi: 10.1159/000488964. Epub 2018 Apr 13.

Abstract

BACKGROUND/AIMS: Physical training has beneficial effects on endothelial function and can influence the regeneration of the endothelial cell. We investigated the effect of physical training on cisplatin (CP)-induced acute kidney injury and assessed the impact of training on endothelial structure and function, and on the inflammatory processes in rats.

METHODS

We injected male Wistar rats subjected to previous physical training in treadmill running (trained, TR) or not (sedentary, SED) with CP (5 mg/kg) (TR+CP and SED+CP groups, respectively). Five days after the injections, blood and urine samples were collected to evaluate renal function and kidneys were harvested for morphological, immunohistochemical, enzyme-linked immunosorbent assay, and analysis of nitric oxide (NO) levels.

RESULTS

Rats treated with CP showed increased levels of plasma creatinine and sodium and potassium fractional excretion. These alterations were associated with increase in tubulointerstitial lesions and macrophage number, reduction of endothelial cells, and increased VEGF, vimentin, and α-smooth muscle actin expression in the outer renal medulla in the SED+CP group. We also found increased levels of renal IL-1β and increased excretion of monocyte chemoattractant protein-1 and transforming growth factor-β compared with controls. These changes were milder in trained rats, associated with increased levels of renal tissue NO, and increased expression of p-eNOS and stromal cell-derived factor-1α (a chemokine involved in kidney repair) in the kidneys of CP-injected trained rats.

CONCLUSIONS

The protective effect of previous training in CP-treated rats was associated with reduced endothelial cell lesions and increased renal production of NO in trained rats.

摘要

背景/目的:体育锻炼对内皮功能具有有益作用,并可影响内皮细胞的再生。我们研究了体育锻炼对顺铂(CP)诱导的急性肾损伤的影响,并评估了锻炼对大鼠内皮结构与功能以及炎症过程的影响。

方法

我们分别向先前进行过跑步机跑步体育锻炼(训练组,TR)或未进行锻炼(久坐组,SED)的雄性Wistar大鼠注射CP(5mg/kg)(分别为TR+CP组和SED+CP组)。注射后五天,采集血液和尿液样本以评估肾功能,并摘取肾脏进行形态学、免疫组织化学、酶联免疫吸附测定以及一氧化氮(NO)水平分析。

结果

接受CP治疗的大鼠血浆肌酐水平升高,钠和钾排泄分数增加。这些改变与SED+CP组肾小管间质损伤增加、巨噬细胞数量增多、内皮细胞减少以及肾外髓质中血管内皮生长因子(VEGF)、波形蛋白和α平滑肌肌动蛋白表达增加有关。与对照组相比,我们还发现肾白细胞介素-1β水平升高,单核细胞趋化蛋白-1和转化生长因子-β排泄增加。这些变化在训练大鼠中较轻,与注射CP的训练大鼠肾脏中肾组织NO水平升高以及磷酸化内皮型一氧化氮合酶(p-eNOS)和基质细胞衍生因子-1α(一种参与肾脏修复的趋化因子)表达增加有关。

结论

先前锻炼对CP治疗大鼠的保护作用与训练大鼠内皮细胞损伤减少以及肾脏NO生成增加有关。

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