Protective effects of aliskiren on ischemia-reperfusion-induced renal injury in rats

Protective effects of aliskiren on ischemia-reperfusion-induced renal injury in rats
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DOI:
10.1016/j.ejphar.2013.08.038
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发表时间:
2013-10-15
影响因子:
5
通讯作者:
Zeng, Chunyu
Zeng, Chunyu
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Zhen;Liu, Yukai;Zeng, Chunyu

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阿利吉仑对心脏和脑缺血再灌注(I/R)损伤的保护作用已有报道。这种保护作用是否延伸到减轻肾PR损伤尚不清楚。因此,我们在本研究中研究了阿利吉仑对肾脏的保护作用。将SD大鼠随机分为4组:假手术对照组、假手术对照加阿利吉仑预处理组、缺血再灌注组和缺血再灌注加阿利吉仑预处理组。通过腔静脉静脉内施用阿利吉仑(3 mg/kg)或媒介物。然后收集血液样品和左肾以检查肾功能、血管紧张素II(Ang II)、细胞凋亡和氧化应激水平。与假手术组相比,I/R组大鼠血清肌酐(SCR)和血尿素氮(BUN)明显升高,并伴有肾小管上皮细胞肿胀、脱落和管型形成等病理改变。I/R组凋亡细胞和白细胞浸润明显多于Sham组。阿利吉仑预处理可减轻I/R所致的肾损伤,即降低SCR和BUN水平,减轻肾组织病理学改变,减少肾组织细胞凋亡和白细胞浸润。I/R损伤还降低了超氧化物歧化酶(SOD)和谷胱甘肽(GSH还原型)水平,这被阿利吉仑预处理阻断。阿利吉仑预处理通过改善氧化应激、减少白细胞浸润和细胞凋亡对肾脏缺血/再灌注损伤发挥保护作用。皇冠版权所有(C)2013由Elsevier BY出版。版权所有© 2016
The protective effect of aliskiren on ischemia-reperfusion (I/R) injury in the heart and brain has been reported. Whether or not this protective effect extends into the alleviation of renal PR injury is not known. Therefore, we investigated the protective effect of aliskiren in the kidney in this study. Sprague-Dawley rats were randomly divided into four groups: sham control group; sham control with aliskiren pretreatment; I/R group and I/R with aliskiren pretreatment. Aliskiren (3 mg/kg) or vehicle was administrated intravenously via vena cava. Blood samples and the left kidneys were then collected to check for renal function, angiotensin II (Ang II), apoptosis and oxidative stress levels. Compared with the sham rats, serum creatinine (SCR) and blood urea nitrogen (BUN) were significantly increased in the I/R rats, accompanied by histopathological damage to the kidney, which included tubular cell swelling, desquamation, and cast formation. There were also more apoptotic cells and leukocyte infiltration in the l/R rats than in the sham rats. Pretreatment with aliskiren ameliorated l/R induced renal injury, i.e. reduced SCR and BUN levels, ameliorated renal histopathological changes, and decreased the apoptosis of cells and leukocyte infiltration in kidney. l/R injury also decreased superoxide dismutase (SOD) and glutathione (GSH-reduced form) levels, which were blocked with the aliskiren pretreatment. Aliskiren pretreatment exerts a protective effect on ischemia/reperhision injury in the kidney, via amelioration of oxidative stress, and reduction in leukocyte infiltration and cellular apoptosis. Crown Copyright (C) 2013 Published by Elsevier BY. All rights reserved,