口服补充L-精氨酸可预防大鼠慢性环孢素肾毒性。

Oral supplementation of L-arginine prevents chronic cyclosporine nephrotoxicity in rats.

作者信息

Yang C W, Kim Y S, Kim J, Kim Y O, Min S Y, Choi E J, Bang B K

机构信息

Department of Internal Medicine, Catholic University Medical College, Seoul, Korea.

出版信息

Exp Nephrol. 1998 Jan-Feb;6(1):50-6. doi: 10.1159/000020504.

DOI:10.1159/000020504

PMID:9523173

Abstract

This study was performed to evaluate the effect of L-arginine (L-Arg) on the prevention of chronic cyclosporine (CsA) nephrotoxicity in rats. Rats pair-fed a low-salt diet (0.05%) were given CsA (15 mg/kg/day s.c.), CsA and L-Arg (L-Arg group, 1.25 g/l water), CsA and N-nitro-L-arginine methyl ester (L-NAME group, 70 mg/l water) or vehicle. After 28 days, the L-Arg group had a higher glomerular filtration rate compared to the CsA (0.42 +/- 0.05 vs. 0.31 +/- 0.06 ml/min/100 g, p < 0.05) and the L-NAME groups (vs. 0.19 +/- 0.04 ml/min/100 g, p < 0.05) and a significantly lower serum creatinine level compared to the CsA (0.70 +/- 0.06 vs. 0.92 +/- 0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21 +/- 0.17 mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injury (TI), and arteriolopathy than the CsA (fibrosis 0.39 +/- 0.14 vs. 0.74 +/- 0.15; TI 1.3 +/- 0.3 vs. 2.0 +/- 0.1; arteriolopathy 33 +/- 7 vs. 48 +/- 17, p < 0.05, respectively) and the L-NAME groups (fibrosis vs. 1.67 +/- 0.32, TI vs. 2.6 +/- 0.3, arteriolopathy vs. 63 +/- 10, p < 0.05, respectively). Plasma renin activity in the L-Arg group was less than in the CsA (18 +/- 2 vs. 23 +/- 3 ng Ang I/ml/h, p < 0.05) and the L-NAME groups (vs. 30 +/- 3 ng Ang I/ml/h, p < 0.05). Nitric oxide production in L-Arg group was higher than in the CsA (24.2 +/- 1.7 vs. 11.1 +/- 1.5 mumol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4 +/- 1.0 mumol/24 h, p < 0.05). In conclusion, the nitric oxide pathway is associated with the pathogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplementation is effective in reducing chronic CsA nephrotoxicity in rats.

摘要

本研究旨在评估L-精氨酸（L-Arg）对预防大鼠慢性环孢素（CsA）肾毒性的作用。对喂食低钠饮食（0.05%）的大鼠给予环孢素（15 mg/kg/天，皮下注射）、环孢素和L-精氨酸（L-Arg组，1.25 g/L水）、环孢素和N-硝基-L-精氨酸甲酯（L-NAME组，70 mg/L水）或赋形剂。28天后，与环孢素组（0.42±0.05 vs. 0.31±0.06 ml/min/100 g，p<0.05）和L-NAME组（vs. 0.19±0.04 ml/min/100 g，p<0.05）相比，L-Arg组的肾小球滤过率更高；与环孢素组（0.70±0.06 vs. 0.92±0.12 mg/dl，p<0.05）和L-NAME组（vs. 1.21±0.17 mg/dl，p<0.05）相比，L-Arg组的血清肌酐水平显著更低。与环孢素组（纤维化0.39±0.14 vs. 0.74±0.15；肾小管损伤（TI）1.3±0.3 vs. 2.0±0.1；小动脉病33±7 vs. 48±17，p均<0.05）和L-NAME组（纤维化vs. 1.67±0.32，TI vs. 2.6±0.3，小动脉病vs. 63±10，p均<0.05）相比，L-Arg组的纤维化、肾小管损伤和小动脉病更少。L-Arg组的血浆肾素活性低于环孢素组（18±2 vs. 23±3 ng Ang I/ml/h，p<0.05）和L-NAME组（vs. 30±3 ng Ang I/ml/h，p<0.05）。L-Arg组的一氧化氮生成高于环孢素组（24.2±1.7 vs. 11.1±1.5 μmol/24 h，p<0.05）和L-NAME组（vs. 8.4±1.0 μmol/24 h，p<0.05）。总之，一氧化氮途径与慢性CsA肾毒性的发病机制相关，外源性补充L-Arg可有效减轻大鼠慢性CsA肾毒性。