Hoyer J R, Ratte J, Potter A H, Michael A F
J Clin Invest. 1972 Oct;51(10):2777-80. doi: 10.1172/JCI107099.
The pathogenesis of aminonucleoside of puromycin (PA) nephrotic syndrome in rats was studied using renal transplantation to separate systemic from renal factors. The nephrotic syndrome was transferred by transplantation of kidneys from rats with established proteinuria. Bilaterally nephrectomized normal rats receiving kidneys removed as early as 15 min after intravenous PA injection (100 mg/kg) of donors also developed proteinuria (602+/-125 mg/24 hr) and a nephrotic syndrome after the usual induction period of 4-7 days observed in this disease. Arterial perfusion of isolated kidneys with PA (50 mg/kg) followed by perfusion with isotonic saline 3 min later and then transplantation to normal bilaterally nephrectomized rats led to a nephrotic syndrome. Urine protein excretion was 494+/-42 mg on the 7th day after transplantation. In contrast, urine protein excretion after transplantation of normal kidneys to normal bilaterally nephrectomized rats was 40+/-20 mg on the 7th day. Exposure of a normal kidney to a nephrotic host environment by transplantation of a normal kidney to a unilaterally nephrectomized PA-injected rat did not transfer the disease to the normal kidney. After removal of the nephrotic kidney 11-13 days after transplantation, proteinuria of the donor kidney was normal (21+/-13 mg on day 15). These studies indicate that pathogenesis of aminonucleoside nephrosis involves programming of the kidney directly by PA within minutes after exposure although increased urinary protein excretion does not occur until several days later.
采用肾移植方法将全身因素与肾脏因素分开，研究了嘌呤霉素氨基核苷（PA）所致大鼠肾病综合征的发病机制。将已出现蛋白尿的大鼠肾脏移植给双侧肾切除的正常大鼠，可导致肾病综合征的转移。在供体静脉注射PA（100mg/kg）后最早15分钟切除的肾脏移植给双侧肾切除的正常大鼠，这些大鼠在本病通常的4 - 7天诱导期后也出现了蛋白尿（602±125mg/24小时）和肾病综合征。用PA（50mg/kg）对离体肾脏进行动脉灌注，3分钟后用等渗盐水灌注，然后移植给双侧肾切除的正常大鼠，可导致肾病综合征。移植后第7天尿蛋白排泄量为494±42mg。相比之下，将正常肾脏移植给双侧肾切除的正常大鼠后，第7天尿蛋白排泄量为40±20mg。将正常肾脏移植给单侧肾切除并注射PA的大鼠，使正常肾脏暴露于肾病宿主环境中，并未将疾病转移至正常肾脏。移植后11 - 13天切除肾病肾脏后，供体肾脏的蛋白尿恢复正常（第15天为21±13mg）。这些研究表明，氨基核苷肾病的发病机制涉及PA在暴露后数分钟内直接对肾脏进行编程，尽管尿蛋白排泄增加直到数天后才出现。
