摘要
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 influence of L-carnitine on expressions of Nrf2 and 7-GCS in renal ischemical reperfnsion injury （RIRI）. Methods Experimental rats were randomized to sham-operation group, ischemia-reperfusion （IR） group and treatment group. A model of RIRI in rats was created in IR group and treatment group. For the rats in treatment group, 2 mL of L-carnitine was injected into a caudal vein before establishment of the model. No IR procedure was done for the rats in steam-operation group. The experimental rats were sacrificed six hours after IR, serum Cr, BUN, Cys C were then detected, and the activity of serum SOD and content of MDA in serum were also measured. The expressions of Nrf2 and γ-GCS in renal tissue were measured by using RT-PCR and Western-blot. Results The levels of Cr, BUN, Cys C and MDA in the treatment group were lower than that in IRgroup, and the activity of SOD was higher （F=8.58-57.42,q=4.06-11.26,P〈0.05）. Compared with the sham-operation group, the expressions of Nrf2, y-GCS mRNA and protein in renal tissue of IR group were higher, and the parameters of above items in the treatment group were even higher than that in IR group （F= 143.53- 241.64, q= 3.76- 13.51,P〈0.05）. Conclusion L-carnitine can relieve ischemical reperfusion injury in kidney, which realizes this target is likely by way of activating Nrf2-ARE and inducing the expression of y-GCS.
出处
《齐鲁医学杂志》
2012年第4期326-328,共3页
Medical Journal of Qilu
基金
山东省医药卫生科技发展计划项目(2011HW032)
