左卡尼汀减轻大鼠肾缺血再灌注损伤及其机制的研究  

Effect of L-carnitine on renal ischemia-reperfusion injury

作　　者：李奎[1] 高健刚[1] 祝海[1] 贾勇[1] 孙延波[1] 侯四川[1] 

机构地区：[1]青岛大学医学院附属青岛市立医院泌尿外科,266071

出　　处：《中华器官移植杂志》2012年第7期430-434,共5页Chinese Journal of Organ Transplantation

基　　金：山东省医药卫生科技发展计划项目（2011HW032）

摘　　要：目的研究左卡尼汀对大鼠肾缺血再灌注损伤（IRI）的影响及其机制。方法将Wistar大鼠分为3组：L组大鼠制成IRI模型，于夹闭肾动静脉前5min及松开动脉夹后30min，分2次经尾静脉注射左卡尼汀，各500mg／kg；I组大鼠制成IRI模型，仅注射生理盐水；C组仅分离双侧。肾动、静脉，注射生理盐水。分别于再灌注后3、6和24h处死各组大鼠。处死前经下腔静脉取血，检测血清肌酐（Cr）、尿素氮（BUN）、超氧化物歧化酶（SOD）及丙二醛（MDA）含量。获取肾组织样本，进行病理学观察；应用逆转录聚合酶链反应检测肾组织核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、γ-谷氨酰半胱氨酸合成酶（7-GCS）的mRNA水平；蛋白质印迹法检测细胞核中Nrf2含量；免疫组织化学法检测肾组织中Nrf2的表达及定位。结果再灌注后3h时，L组与I组血清Cr和BUN均高于C组（P〈0．01）；再灌注后6h时，L组血清Cr和BUN高于C组（P〈0．01），而低于I组（P〈0．01）；再灌注后24h时，L组血清Cr和BUN仍低于I组（P〈0．05）。再灌注后6和24h时，L组与I组SOD水平低于C组（P〈0．05），MDA水平高于C组（P〈0．05）。再灌注后各时间点，L组SOD水平均高于I组（P〈0．05），MDA水平均低于I组（P〈0．05）。再灌注后24h时，L组肾组织病理改变较I组轻。再灌注后6h时，1组Nrf2、HO-1、γ-CX；S的mRNA相对含量均高于C组（P〈0．05），而L组各基因mRNA的相对含量高于I组（P〈0．05）。L组细胞核内Nrf2的相对含量高于I组（P〈0．05）。结论左卡尼汀可减轻大鼠肾脏IRI，其机制可能与激活Nrf2-ARE通路，进而增强下游抗氧化基因的表达有关。Objective To investigate the effect of L-camitine on renal ischemia-repeffusion （IR） injury （IRI） and Nff2-ARE signaling pathway in rats. Methods Rats were randomly separated into the following experimental groups： control group （group C）, IRI group （group I） and L-carnitine group （group L）. Rats accepted no treatment of ischemic reperfusion in group C. In groups I and group L, the renal IRI model was established. L-carnitine was injected through the tail vein in group L, while the equal volume of saline was injected in group C and group I. Rats were killed at 3, 6, and 24 h after IR. The levels of serum creatinine （Cr） and blood urea nitrogen （BUN）, the activity of superoxide dismutase （SOD） and the content of malonaldehyde （MDA） in serum were measured. The histopathological lesions were observed in renal tissues after 24-h LR. RT-PCR was used to detect the levels of NrI2, HO-1 and γ-CCS mRNA. Western blotting and immunohistochemistry were used to detect the levels and localization of Nff2 protein in renal tissues after 6-h IR. Results The levels of Cr and BUN in group I and group L were higher than those in group C at 3 h alter At 6 h after IR, the levels of Cr and BUN in group L were lower than those in group I （P（0. 01）. At 24 h after IR, the levels of Cr and BUN in group L were still lower than those in group I though both of them were reduced （P〈0. 05）. At all time points, the activity of SOD in group L was higher and the content of MDA was lower than those in group I （P〈0. 05）. As compared with group I, the renal histopathological lesions were alleviated in group L at 24 h after IR. At 6 h after IR, levels of Nff2, HO-1, γ-GCS mRNA and Nff2 protein in group I were increased as compared with group C, but decreased as compared with group L. Beyond that, the expression of nuclear Nrf2 protein in group L was higher than that in group I. Conclusion L-carnitine can protects the kidney against IRI significantly, which may be due to the up-regulated expres

关 键 词：左卡尼汀 肾 缺血再灌注损伤 NF-E2相关因子2 

分 类 号：R285.5[医药卫生—中药学]