Ziypak Tevfik, Halici Zekai, Alkan Erdal, Akpinar Erol, Polat Beyzagul, Adanur Senol, Cadirci Elif, Ferah Irmak, Bayir Yasin, Karakus Emre, Mercantepe Tolga
Department of Urology, Faculty of Medicine, Ataturk University , Erzurum , Turkey .
Ren Fail. 2015 Mar;37(2):343-54. doi: 10.3109/0886022X.2014.991327. Epub 2014 Dec 19.
To determine the protective effect of aliskiren on ischemia-reperfusion (I/R) injury in a rat renal (I/R) model.
Rats were randomly divided into five groups: sham control group; sham control with aliskiren pretreatment; I/R group and I/R with two doses of aliskiren pretreatment. Rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Aliskiren (50 and 100 mg/kg) was administered orally by gavage 24 and 1 h prior to ischemia. After 24 h reperfusion, kidney samples were taken for the determination of malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione (GSH) activity and histological evaluation. The level of serum creatinine (SCR) and blood urea nitrogen (BUN), renin and angiotensin II (AT-2) was measured in serum samples.
Kidneys from I/R groups showed significant increase in MDA level and significant decrease in GSH, and SOD activity. IL-1β, iNOS and NFkB gene expression significantly increased in the I/R groups in the rat kidney tissue. Aliskiren treatment showed a significant down-regulatory effect on IL-1β, iNOS and NFkB mRNA expression. Compared with the sham group, SCR and BUN, renin and AT-2 were significantly increased in the I/R rats, accompanied by histopathological damage to the kidney.
Pretreatment with aliskiren ameliorated I/R-induced renal injury through decreasing nitric oxide and AT-2 levels and by the reduction of injury induced by I/R injury and ameliorated renal histopathological molecular and biochemical changes.
在大鼠肾缺血再灌注（I/R）模型中确定阿利吉仑对缺血再灌注损伤的保护作用。
将大鼠随机分为五组：假手术对照组；阿利吉仑预处理的假手术对照组；I/R组以及阿利吉仑两剂量预处理的I/R组。大鼠进行单侧肾切除，肾蒂阻断45分钟，随后再灌注24小时。在缺血前24小时和1小时经口灌胃给予阿利吉仑（50和100mg/kg）。再灌注24小时后，取肾组织样本测定丙二醛（MDA）水平、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）活性并进行组织学评估。测定血清样本中的血清肌酐（SCR）、血尿素氮（BUN）、肾素和血管紧张素II（AT-2）水平。
I/R组的肾脏MDA水平显著升高，GSH和SOD活性显著降低。大鼠肾组织I/R组中白细胞介素-1β（IL-1β）、诱导型一氧化氮合酶（iNOS）和核因子κB（NFkB）基因表达显著增加。阿利吉仑治疗对IL-1β、iNOS和NFkB mRNA表达有显著下调作用。与假手术组相比，I/R大鼠的SCR、BUN、肾素和AT-2显著升高，同时伴有肾脏组织病理学损伤。
阿利吉仑预处理通过降低一氧化氮和AT-2水平、减轻I/R损伤诱导的损伤以及改善肾脏组织病理学、分子和生化变化，减轻了I/R诱导的肾损伤。
