氨甲酰化促红细胞生成素对慢性肾衰竭合并急性肾损伤大鼠肾脏的保护作用  

Renal protective effects of carbamylated erythropoietin in chronic renal failure rats complicated with acute kidney injury

作　　者：梅艳[1] 洪权[1] 马倩 张杰[1] 谢院生[1] 蔡广研[1] 陈香美[1] Mei Yan;Hong Quan;Ma Qian;Zhang jie;Xie yuansheng;cai guangyan;chen Xiangmei;Hong Quan;Ma Qian(Department o f Nephrology,Chinese General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing 100853,China)

机构地区：[1]解放军总医院肾脏病科解放军肾脏病研究所肾脏疾病国家重点实验室国家慢性肾病临床医学研究中心,北京100853

出　　处：《中华肾病研究电子杂志》2018年第3期122-125,共4页Chinese Journal of Kidney Disease Investigation（Electronic Edition）

基　　金：国家自然科学基金(81470949;81670671;82473531);国家科技支撑计划(2015BAI12B06)

摘　　要：目的观察氨甲酰化促红细胞生成素(carbamylated erythropoietin,CEPO)对慢性肾脏病(CKD)合并急性肾损伤(AKI)大鼠模型的肾脏保护作用。方法取健康雄性SD大鼠(450±20 g)39只,随机分为3组,首先制作5/6肾切除大鼠慢性肾衰模型,10 d后确认大鼠慢性肾衰竭模型造模成功。在该慢性肾衰竭模型大鼠双后肢肌肉按照8 ml/kg的剂量注射50%甘油制作合并急性肾损伤模型。第11,12,13天向各组注射:生理盐水(NS)组:腹腔注射生理盐水;促红细胞生成素(EPO)组:按照5 000 U/kg的剂量向大鼠腹腔内注射EPO;CEPO组:按照5 000 U/kg的剂量进行腹腔注射CEPO。在第1,5,10,11,13,17天对大鼠的体重、血压进行检测,同时尾静脉采血对红细胞比容、血肌酐、尿素氮进行检测,留取肾组织进行病理学PAS检测。用SPSS 19.0统计软件对实验数据进行统计学处理,P<0.05被认为差异有统计学意义。结果与生理盐水注射组比较,CEPO组和EPO组可缓解大鼠体重的减轻幅度(F=8.19,F=6.84,P<0.05),可保护大鼠肾功能,降低大鼠血肌酐(F=5.12,F=13.72,P<0.05)和血尿素(F=4.63,F=12.78,P<0.05)的水平,减轻肾脏小管病理损伤(F=9.14,F=12.73,P<0.05),并且CEPO组能显示出更明显的作用(P<0.05),CEPO相对于EPO能够缓解升高红细胞比容的副作用(F=8.27,P=0.019)。结论 CEPO对CKD合并AKI模型大鼠能起到明显的肾脏保护作用,并且相对于EPO治疗能降低引起红细胞比容升高的副作用。Objective To observe the renal protective effects of carbamylated erythropoietin（ CEPO） in rats with chronic kidney disease（ CKD） complicated with acute kidney injury（ AKI）. Methods Thirty-nine healthy male SD rats（ 450 ± 20 g） were randomly divided into three groups. Firstly,the model of chronic renal failure was made by 5/6 nephrectomy in rats,and was confirmed 10 days later. Afterwards,the model of complicated AKI was made by injection in the hind limb muscle with 50% glycerol at a dose of 8 ml/kg. On the 11th,12th,and 13th day,each group was treated with intraperitoneal injection of normal saline（ NS group）,erythropoietin at a dose of 5 000 U/kg（ EPO group）,and CEPO at a dose of 5 000 U/kg（ CEPO group）. On the 1st,5th,10th,11th,13th,and 17th day,the body weight and blood pressure of the rats were detected. At the same time,blood from the tail vein was used to detect hematocrit,serum creatinine,and urea nitrogen,and the renal tissues were taken for pathological periodic acid-Schiff（ PAS）staining. The experimental data were processed with SPSS 19. 0 statistical software. P〈0. 05 was considered statistically significant. Results Compared with the NS group,the CEPO group and the EPO group relieved the weight loss of rats（ F = 8. 19,F = 6. 84,P〈0. 05）,reduced the levels of Scr（ F = 5. 12,F = 13. 72,P〈0. 05） and BUN（ F = 4. 63,F = 12. 78,P〈0. 05）,and reduced the renal tubular pathological damage（ F = 9. 14,F = 12. 73,P〈0. 05）. The CEPO group＇s effects were more obvious than those of the EPO group（ P〈0. 05）. And CEPO relieved the increase of hematocrit,the side effect of EPO（ F = 8. 27,P =0. 019）. Conclusions CEPO showed significant renal protective effects in the CKD rat model complicated with AKI. The CEPO treatment could also reduce the increased level of hematocrit.

关 键 词：慢性肾脏疾病 急性肾损伤 氨甲酰化促红细胞生成素 

分 类 号：R692.5[医药卫生—泌尿科学]