Kasap Belde, Soylu Alper, Kuralay Filiz, Sarioglu Sülen, Kiray Müge, Tuğyan Kazim, Türkmen Mehmet, Kavukcu Salih
Department of Pediatrics, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
Pediatr Nephrol. 2008 Nov;23(11):1991-9. doi: 10.1007/s00467-008-0903-1. Epub 2008 Jul 11.
The aim of our study was to determine the effect of recombinant human erythropoietin (rhEPO) on cyclosporine (CsA) nephrotoxicity. Twenty-six female Wistar rats were injected with 15 mg/kg subcutaneous CsA and intraperitoneal saline/rhEPO for 28 days. Four groups were formed: Group 1 (n = 5), a control group; Group 2 (n = 7), CsA + saline; Group 3 (n = 7), CsA + low dose (20 U/kg per day) rhEPO; Group 4 (n = 7), CsA + high dose (100 U/kg per day) rhEPO. Body weights, creatinine clearance, urinary protein/creatinine, hematocrit, serum creatinine levels, histopathological parameters, apoptosis and lipid peroxidation tests were compared between the three groups. Body weights and renal functions were similar in Groups 2, 3 and 4 rats but significantly lower than the values found for the control group at the end of the study. The hematocrit was significantly different between the four groups, showing a positive association with the strength of the injected rhEPO doses. Tubular and arteriolar damage was significantly lower in Groups 3 and 4 rats than in Group 2 rats, while chronic changes were similar between the three groups. TUNEL-positive cells and thiobabarbituric acid reacting substance (TBARS) levels were significantly higher in Group 2 rats, whereas superoxide dismutase levels were significantly lower in Group 2 rats than in those of the other three groups. Low or high dose rhEPO had no significant protective effects on body weight, renal functions, chronic fibrotic changes, but both doses reduced tubular and arteriolar changes, apoptotis and oxidative stress.
我们研究的目的是确定重组人促红细胞生成素(rhEPO)对环孢素(CsA)肾毒性的影响。26只雌性Wistar大鼠皮下注射15mg/kg CsA,并腹腔注射生理盐水/rhEPO,持续28天。分为四组:第1组(n = 5)为对照组;第2组(n = 7)为CsA + 生理盐水组;第3组(n = 7)为CsA + 低剂量(每天20U/kg)rhEPO组;第4组(n = 7)为CsA + 高剂量(每天100U/kg)rhEPO组。比较三组之间的体重、肌酐清除率、尿蛋白/肌酐、血细胞比容、血清肌酐水平、组织病理学参数、细胞凋亡和脂质过氧化试验。第2、3和4组大鼠的体重和肾功能相似,但在研究结束时显著低于对照组的值。四组之间的血细胞比容有显著差异,与注射的rhEPO剂量强度呈正相关。第3和4组大鼠的肾小管和小动脉损伤明显低于第2组大鼠,而三组之间的慢性变化相似。第2组大鼠的TUNEL阳性细胞和硫代巴比妥酸反应物质(TBARS)水平显著更高,而第2组大鼠的超氧化物歧化酶水平显著低于其他三组。低剂量或高剂量rhEPO对体重、肾功能、慢性纤维化变化没有显著的保护作用,但两种剂量均减少了肾小管和小动脉变化、细胞凋亡和氧化应激。