促红细胞生成素联合缺血预处理对肾缺血再灌注损伤的保护作用

Effects of Erythropoietin Combined with Ischemic Preconditioning on Renal Ischemia-Reperfusion Injury in Rats

目的:评价促红细胞生成素(EPO)联合缺血预处理对大鼠肾缺血再灌注损伤的影响。方法:健康SD雄性大鼠30只,200-220g,随机分为5组(n=6):假手术组(S组)、缺血再灌注组(I/R组)、缺血预处理组(IP组)、促红细胞生成素预处理组(EPO组)、缺血预处理联合促红细胞生成素预处理组(IP+EPO组)。各组于术后24h测定血清肌酐(Cr)和尿素氮(BUN)水平;测定肾组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及髓过氧化物酶(MPO)活性;观察肾组织病理学结果;检测肾小管上皮细胞凋亡情况。结果:与I/R组比较,IP组、EPO组、IPC+EPO组血清中Cr和BUN浓度,组织MDA含量及MPO活性降低,组织SOD活性升高,细胞凋亡减少(P<0.05),病理损伤减轻。与IP组和EPO组比较,IP+EPO组血清Cr和BUN的浓度降低,肾组织SOD活性升高,MDA含量与凋亡指数降低(P<0.05),病理损伤减轻。对于MPO含量,IP+EPO组相比较IP组有统计学意义,而相比较EPO组无统计学意义(P>0.05)。结论:缺血预处理联合促红细胞生成素预处理可以进一步加强大鼠肾缺血再灌注损伤后肾功能的保护,其机制可能是联合处理在抗氧化损伤、抗细胞凋亡方面发挥了叠加效应。

Objective： To evaluate the effect of erythropoietin （EPO） combined with ischemic preconditioning on the renal ischemia-reperfusion injury in rats. Methods. Thirty healthy male SD rats weighing 200-220 g were randomly assigned into five groups （n= 6 each） ; sham operation group （group S）, ischemia-reperfusion group （group I/R）, ischemic preconditioning group （group IP）, EPO pretreatment group （group EPO）, and ischemic preconditioning combined with EPO pre- treatment group （group IP＋EPO）. At the end of 24 h after operation, blood samples were obtained for determination of blood creatinine （Cr） and urea nitrogen （BUN） concentrations. Left kidneys were removed for determination of SOD and MPO activity, MDA concentrations, and apoptosis in the renal tubular epithelial cells. The changes of renal tissue were examined by micro- scope. Results. Compared with group I/R, serum concentrations of Cr and BUN, MDA content, MPO activity, and apoptosis index significantly decreased, whereas SOD activity increased and pathological damage mitigated in the group IP, group EPO and group IP＋EPO （P〈0. 05）.Compared with that respectively in group IP and group EPO, serum concentrations of Cr and BUN, MDA content, apoptosis index significantly decreased, and SOD activity increased in the group IP＋EPO （P〈0.05）. No difference was found in MPO activity between the group IP＋ EPO and group EPO （P〈0.05）. Conclusion： Ischemic preconditioning combined with EPO pretreatment can enhance renal protection after renal ischemia-reperfusion injury in rats. They may play a superimposed effect in offering antioxidant benefits and inhibit the apoptosis in the renal tubular epithelial cells.