摘要
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.
出处
《广西医学》
CAS
2014年第12期1688-1691,共4页
Guangxi Medical Journal
基金
广西医药卫生科研课题(Z2008292)
关键词
肾脏缺血
肾灌注损伤
重组人促红细胞生成素
最佳剂量
最佳时机
Renal ischemia
Renal perfusion injury
Recombinant human erythropoietin
Optimal dosing
Optimal timing
