左卡尼汀对肾缺血再灌注损伤的抗氧化作用及其机制

目的研究左卡尼汀对大鼠肾缺血再灌注损伤的抗氧化作用并探讨其机制。方法将大鼠随机分为3组：对照组（C组）,缺血再灌注组（IR组）,左卡尼汀组（LC组）。C组不予缺血再灌注处理,IR组及LC组建立肾脏IR模型。再灌注6h后检测各组血清肌酐（Cr）和尿素氮（BUN）水平;测定肾组织超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量;RT-PCR检测肾组织核因子E2相关因子2（Nrf2）、血红素氧化酶-1（HO-1）mRNA含量;Western-blot检测各组肾组织Nrf2及HO-1蛋白表达水平。结果 LC组血清Cr、BUN水平低于IR组（74.17±12.80）μmol/L、（24.28±2.58）mmol/L vs.（112.83±17.45）μmol/L、（35.13±6.01）mmol/L],差异具有统计学意义（P〈0.01）。LC组肾组织SOD活性高于IR组（39.55±6.61）kU/g vs.（28.05±4.37）kU/g],差异具有统计学意义（P〈0.01）;MDA显著降低于IR组（4.15±0.69）μmol/g vs.（6.12±1.08）μmol/g],差异具有统计学意义（P〈0.01）。IR组Nrf2、HO-1mRNA及蛋白表达水平高于C组（P〈0.01）,低于LC组（P〈0.01）。结论左卡尼汀对肾脏缺血再灌注损伤具有明显保护作用,其机制可能为激活Keapl-Nrf2-ARE通路进而诱导HO-1的表达。

The antioxidation of L-carnitine on renal ischemia-reperfusion injury and its underlying mechanism

Objective To investigate the antioxidation of L-carnitine on renal ischemia-reperfusion injury(IRI) and its underlying mechanism.Methods Eighteen rats were randomly divided into three groups:control group(group C),ischemia-reperfusion group(group IR) and L-carnitine group(group LC).Rats in group C received no treatment of ischemic reperfusion.In group IR and LC,the renal ischemia-reperfusion(IR) model was established.Six hours after IR,the levels of serum creatinine(Cr) and urea nitrogen(BUN),the activities of superoxide dismutase(SOD) and the content of malonaldehyde(MDA) in serum were measured.RT-PCR was used to detect the levels of Nrf2 and HO-1 mRNA and Western-blot was used to detect the levels of Nrf2 and HO-1 protein in renal tissues.Results The levels of Cr and BUN in group LC were lower than those in group IR(P<0.01),which were(74.17±12.80) μmol/L and(24.28±2.58) mmol/L vs.(112.83±17.45) μmol/L and(35.13±6.01) mmol/L.The activity of SOD in group LC was higher but the content of MDA was lower than those in group IR(P<0.01),which were(39.55±6.61) kU/g and(4.15±0.69) μmol/g vs.(28.05±4.37) kU/g and(6.12±1.08) μmol/g,respectively.The mRNA and protein expression of Nrf2 and HO-1 in group IR increased as compared with group C(P<0.01),but decreased as compared with group LC(P<0.01).Conclusions L-carnitine can protect ischemia-reperfusion injury significantly,which might be due to the hyperexpression of HO-1 induced by activated Keapl-Nrf2-ARE signaling pathway.