Saito T, Sumithran E, Glasgow E F, Atkins R C
Department of Nephrology, Prince Henry's Hospital, Melbourne, Australia.
Kidney Int. 1987 Nov;32(5):691-9. doi: 10.1038/ki.1987.262.
An experimental model of focal segmental glomerular sclerosis (FSGS) was developed in rats by the combined administration of puromycin-aminonucleoside (AMNS) and protamine sulfate (PS). Male Sprague-Dawley rats, uninephrectomized three weeks before, received daily injections of subcutaneous AMNS (1 mg/100 g body wt) and intravenous PS (2 separated doses of 2.5 mg/100 g body wt) for four days. The series of injections were repeated another three times at 10 day intervals. The animals were sacrificed on days 24, 52, and 80. They developed nephrotic syndrome and finally renal failure. The time-course curve of creatinine clearance dropped and showed significant difference (P less than 0.01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end-stage renal disease.
通过联合给予嘌呤霉素氨基核苷（AMNS）和硫酸鱼精蛋白（PS），在大鼠中建立了局灶节段性肾小球硬化（FSGS）的实验模型。雄性Sprague-Dawley大鼠在三周前进行单侧肾切除术，连续四天每日皮下注射AMNS（1mg/100g体重）和静脉注射PS（分两次给药，每次2.5mg/100g体重）。每隔10天重复注射该系列药物三次。在第24、52和80天处死动物。它们出现了肾病综合征，最终发展为肾衰竭。肌酐清除率的时间进程曲线下降，与每个对照组（如单独注射AMNS、单独注射PS或注射生理盐水）相比有显著差异（P<0.01）。它们的肾小球呈现出进行性FSGS的变化。初始阶段的超微结构研究显示，在肾小球基底膜外侧显著缺乏灌注钌红颗粒，上皮细胞质有明显变化。因此，提示给予PS可增强AMNS对肾小球的毒性，并容易在大鼠中产生进行性FSGS，导致终末期肾病。
