促红细胞生成素治疗大鼠肾脏缺血再灌注损伤最佳剂量及时机的探讨

Optimal Dosing and Timing of Erythropoietin for Treatment of Renal Ischemia-reperfusion Injury in Rats

目的探讨重组人促红细胞生成素(r Hu EPO)治疗大鼠肾脏缺血再灌注性损伤的最佳剂量及时机。方法将60只SD大鼠随机分为6组,每组10只,假手术组、模型组、高剂量24(高24)组:造模后腹腔注射r Hu EPO 5 000 U/kg,24 h后取肾标本;低剂量24(低24)组:r Hu EPO 2 500 U/kg,24 h取肾脏标本;高剂量48(高48)组:r Hu EPO 5 000 U/kg,48 h取肾标本;低剂量48(低48)组:r Hu EPO 2 500 U/kg,24 h后追加2 500 U/kg,48 h取肾标本。检测血清尿素氮(BUN)、肌酐水平(Scr)、肾组织中磷酸化应激活化蛋白激酶(p-JNK)的表达及肾小管上皮细胞凋亡情况。结果与假手术组相比,其他5组大鼠BUN、Scr明显升高,凋亡加重,p-JNK表达增多;与模型组相比,各r Hu EPO治疗组肾功能明显好转,肾功能高24组好于低24组,高48组好于低48组(P<0.05)。结论及时一次大剂量应用r Hu EPO对大鼠肾脏具有更好的保护作用,可能是通过调节p-JNK等因子表达以减少凋亡的发生,而达到改善肾脏病理性损伤。

Objective To explore the optimal dosing and timing of recombinant human erythropoietin（ rHuEPO） for the treatment of renal ischemia-reperfusion injury in rats. Methods Sixty SD rats were randomly divided into six groups,with 10 rats in each group,including sham operation group,ischemia reperfusion injury group（ model group）,high-dose 24 group,low-dose 24 group,high-dose 48 group,and low-dose 48 group. The rats in the high-dose 24 group received the injection of rHuEPO at a dose of 5000 U / kg and then renal specimen sampling 24 hours later. The rats in the low-dose 24 group received the injection of rHuEPO at a dose of 2 500 U / kg and then renal specimen sampling 24 hours later. The rats in the high-dose 48 group received the injection of rHuEPO at a dose of 5 000 U / kg and then renal specimen sampling 48 hours later. The rats in the low-dose 48 group received the injection of rHuEPO at a dose of 2 500 U / kg,and then were give an additional injection of rHuEPO at a dose of 2500 U / kg 24 hours later,followed by the renal specimen sampling 48 hours later. To detect the levels of blood urea nitrogen（ BUN） and serum creatinine（ Scr）,the expression of phosphorylated c-Jun N-terminal kinase（ p-JNK） in the kidney tissues and the renal tubular cell apoptosis. Results Compared with sham group,the rats in other 5 groups showed the significantly higher levels of BUN and Scr,apoptosis increased,and p-JNK expression increased. Compared with model group,the rats in the other groups with rHuEPO therapy showed a significant improvment of renal function. The renal function of rats in the high-dose24 group was superior to that in the low-dose 24 group,and the renal function of rats in the high-dose 48 group was superior to that in the low-dose 48 group（ P〈0. 05）. Conclusion The timely and sufficient large-dose of rHuEPO has a protective effect on rats＇ kidney,which might contribute to the improvement of renal pathological injury by regulating the p-JNK expression and decreasing the apoptosis.