环孢素治疗嘌呤霉素肾病中抗氧化酶抑制和蛋白尿的改善

Amelioration of antioxidant enzyme suppression and proteinuria in cyclosporin-treated puromycin nephrosis.

作者信息

Wang J S, Yang A H, Chen S M, Young T K, Chiang H, Liu H C

机构信息

Department of Pathology, Veterans General Hospital-Taipei VACRS, Taiwan, ROC.

出版信息

Nephron. 1993;65(3):418-25. doi: 10.1159/000187523.

DOI:10.1159/000187523

PMID:8289993

Abstract

The effect of cyclosporin (CS) on intrinsic glomerular level of antioxidants in puromycin aminonucleoside (PAN) nephrosis was examined. A single intravenous dose of PAN (50 mg/kg body weight) given to Sprague-Dawley rats resulted in marked proteinuria. Ten days after PAN injection, the rats were treated with daily intraperitoneal injection of CS (10 mg/kg body weight/day) for 10 days. PAN-treated rats without CS treatment (PAN rats) had significantly lower activities of glomerular superoxide dismutase (SOD) and catalase (CAT) than normal rats (p < 0.05, respectively). When compared with PAN rats, CS-treated PAN rats had significantly less proteinuria and higher activities of glomerular SOD and CAT (p < 0.01 and p < 0.05, respectively). Significant elevation of glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in CS-treated PAN rats. Moreover, segmental sclerosis with capsular adhesion, hyalinosis, epithelial cell foot process fusion and microvillous transformation seen in PAN rats were apparently attenuated in CS-treated PAN rats. When compared with normal rats, rats receiving CS only had a significantly higher CAT activity and MDA level (p < 0.01 and p < 0.05, respectively). Assessment of glomerular reduced glutathione revealed no significant differences among PAN rats, CS-treated PAN rats, normal rats, and rats receiving only CS. These data indicate that glomerular antioxidant enzyme activities are modulated by CS.

摘要

研究了环孢素（CS）对嘌呤霉素氨基核苷（PAN）肾病模型肾小球内抗氧化剂水平的影响。给Sprague-Dawley大鼠单次静脉注射PAN（50mg/kg体重）可导致明显蛋白尿。PAN注射10天后，大鼠每天腹腔注射CS（10mg/kg体重/天），持续10天。未接受CS治疗的PAN处理大鼠（PAN大鼠）的肾小球超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性显著低于正常大鼠（分别为p<0.05）。与PAN大鼠相比，CS处理的PAN大鼠蛋白尿明显减少，肾小球SOD和CAT活性更高（分别为p<0.01和p<0.05）。CS处理的PAN大鼠不存在PAN大鼠特有的肾小球丙二醛（MDA）水平显著升高的情况。此外，PAN大鼠中出现的节段性硬化伴包膜粘连、玻璃样变性、上皮细胞足突融合和微绒毛转化在CS处理的PAN大鼠中明显减轻。与正常大鼠相比，仅接受CS的大鼠CAT活性显著更高，MDA水平也显著更高（分别为p<0.01和p<0.05）。对肾小球还原型谷胱甘肽的评估显示，PAN大鼠、CS处理的PAN大鼠、正常大鼠和仅接受CS的大鼠之间无显著差异。这些数据表明，肾小球抗氧化酶活性受CS调节。