Kinaci M Kenan, Erkasap Nilufer, Kucuk Aysegul, Koken Tulay, Tosun Murat
Department of Physiology, Eskisehir Osmangazi University Medical Faculty, Eskisehir;
Exp Ther Med. 2012 Feb;3(2):249-254. doi: 10.3892/etm.2011.382. Epub 2011 Nov 16.
The aim of this study was to investigate the effects of quercetin on nitric oxide synthase (NOS), nuclear factor-κB (NF-κB) and apoptosis in renal ischemia/reperfusion (I/R) injury in rats. A total of 42 Sprague-Dawley rats were divided into three groups. The control, I/R and I/R+quercetin (I/R+Q) groups were treated with quercetin (50 mg/kg intraperitoneal) 1 h prior to the induction of ischemia. Tissue malondialdehyde (MDA) and glutathione (GSH) levels were determined by high-performance liquid chromatography (HPLC). p53, endothelial NOS (eNOS) and NF-κB expression were assessed immunohistochemically, and apoptosis assesment was performed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay. The mRNA levels of inducible NOS (iNOS) in renal tissue were determined by real-time polymerase chain reaction (RT-PCR). MDA levels were significantly decreased in the quercetin group compared to the I/R group. However, GSH levels were significantly increased with quercetin treatment in the I/R group. Histological results, the number of apoptotic and p53-positive cells, NF-κB and eNOS expression levels were significantly decreased in the quercetin treatment group compared to the I/R group. iNOS gene expression increased in the I/R group, but no significant difference was found between the I/R and quercetin treatment groups. Therefore, quercetin not only has antioxidant and anti-apoptotic activities, but also has an inhibitory effect on eNOS and NF-κB for renal tissue protection during I/R injury in rats. Therefore, quercetin may be a promising renoprotective therapeutic agent.
本研究旨在探讨槲皮素对大鼠肾脏缺血/再灌注(I/R)损伤中一氧化氮合酶(NOS)、核因子-κB(NF-κB)及细胞凋亡的影响。将42只Sprague-Dawley大鼠分为三组。对照组、I/R组和I/R+槲皮素(I/R+Q)组在缺血诱导前1小时腹腔注射槲皮素(50 mg/kg)。采用高效液相色谱法(HPLC)测定组织丙二醛(MDA)和谷胱甘肽(GSH)水平。免疫组织化学法评估p53、内皮型NOS(eNOS)和NF-κB的表达,采用末端脱氧核苷酸转移酶dUTP缺口末端标记法(TUNEL)检测细胞凋亡。通过实时聚合酶链反应(RT-PCR)测定肾组织中诱导型NOS(iNOS)的mRNA水平。与I/R组相比,槲皮素组MDA水平显著降低。然而,I/R组经槲皮素处理后GSH水平显著升高。组织学结果显示,与I/R组相比,槲皮素治疗组凋亡细胞和p53阳性细胞数量、NF-κB和eNOS表达水平显著降低。I/R组iNOS基因表达增加,但I/R组与槲皮素治疗组之间未发现显著差异。因此,槲皮素不仅具有抗氧化和抗凋亡活性,而且对大鼠I/R损伤期间的肾组织保护中eNOS和NF-κB具有抑制作用。因此,槲皮素可能是一种有前景的肾脏保护治疗药物。