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目的研究左卡尼汀对大鼠肾脏缺血再灌注损伤中核因子相关因子2(Nrf2)、γ-谷氨酰半胱氨酸合成酶(γ-GCS)表达的影响。方法将大鼠随机分为假手术组、缺血再灌注组及治疗组。缺血再灌注组及治疗组建立肾脏缺血再灌注损伤模型,治疗组在缺血再灌注损伤模型建立前后尾静脉注射左卡尼汀2mL。假手术组不行缺血再灌注处理。再灌注6h后处死大鼠,取血检测血清肌酐(Cr)、尿素氮(BUN)及胱抑素C(Cys C)的水平,并测定血清超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。应用RT-PCR及Western-blot方法检测肾组织中Nrf2和γ-GCS的表达水平。结果治疗组Cr、BUN、Cys C及MDA水平显著低于缺血再灌注组,SOD活性显著高于缺血再灌注组(F=8.58～57.42,q=4.06～11.26,P<0.05);与假手术组相比,缺血再灌注组肾组织中Nrf2、γ-GCSmRNA及蛋白表达水平显著升高,而治疗组肾组织中上述指标较缺血再灌注组显著增高(F=143.53～241.64,q=3.76～13.51,P<0.05)。结论左卡尼汀可减轻肾脏缺血再灌注损伤,其机制可能为通过激活Nrf2-ARE通路进而诱导γ-GCS的表达而实现的。
Objective To investigate the effects of levocarnitine on the expression of nuclear factor related factor 2 (Nrf2) and γ-glutamylcysteine synthase (γ-GCS) during renal ischemia-reperfusion injury in rats. Methods The rats were randomly divided into sham operation group, ischemia reperfusion group and treatment group. The model of renal ischemia-reperfusion injury was established in ischemia-reperfusion group and treatment group, and 2 mL of levocarnitine was injected into caudal vein before and after ischemia-reperfusion injury model was established in treatment group. Sham-operated group did not deal with ischemia-reperfusion. Six hours after the reperfusion, the rats were sacrificed and the levels of serum creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (Cys C) were measured and the activities of serum superoxide dismutase (SOD) and malondialdehyde (MDA) content. The expression of Nrf2 and γ-GCS in renal tissues was detected by RT-PCR and Western-blot. Results The levels of Cr, BUN, Cys C and MDA in the treatment group were significantly lower than those in the ischemia / reperfusion group (P <0.05). The activity of SOD in the treatment group was significantly higher than that in the ischemia / reperfusion group (F = 8.58-57.42, The expression of Nrf2 and γ-GCS mRNA and protein in renal tissue of ischemic reperfusion group was significantly higher than that in sham-operated group, while the above indexes in treatment group were significantly higher than those in ischemia-reperfusion group (F = 143.53-241.64, q = 3.76 ~ 13.51, P <0.05). Conclusion L-carnitine can reduce renal ischemia-reperfusion injury, and its mechanism may be through activation of Nrf2-ARE pathway and then induce the expression of γ-GCS.