Pak K, Tomoyoshi T, Nomura Y, Okabe T
Department of Urology, Shiga University of Medical Science.
Hinyokika Kiyo. 1987 Dec;33(12):1966-74.
Cyclosporin (CS) is a potent immunosuppressant that has been used in organ transplantation, but it has a serious nephrotoxic effect. To investigate its effects on renal function and structure, we carried out biochemical and morphological examinations in rats. Male Wistar rats each weighing 250 g were used. Rats were given various dose regimens (100, 50, 25 and 10 mg/kg/day) of CS orally over a 21-day period. All the rats were killed and examined on the 22nd day. Blood urea nitrogen (BUN), serum and urinary creatinine and urinary N-acetyl-s-D-glucosaminidase (NAG) were measured before administration and on the 7th, 14th and 21st day after administration. Kidneys were examined with light and electron microscopes. All rats that had received 100 mg/kg/day CS died within 12 days after a severe loss in body weight. Rats that had received 50 or 25 mg/kg/day CS had lost weight which never returned to the weight before administration. A high CS dose caused a significant elevation of BUN unaccompanied by a corresponding rise in serum creatinine. Reduction of creatinine clearance was not prominent during the experimental course. Although the urinary NAG activity was increased in high dose groups, the elevation was not related to dose. Morphological alterations were confined to the proximal tubuli and they consisted of tubular cell vacuolation and increased number of lysosomes. However, these alterations were mild and not related to the CS dose.
环孢素（CS）是一种强效免疫抑制剂，已用于器官移植，但它具有严重的肾毒性作用。为了研究其对肾功能和结构的影响，我们对大鼠进行了生化和形态学检查。使用体重为250 g的雄性Wistar大鼠。在21天的时间内，给大鼠口服不同剂量方案（100、50、25和10 mg/kg/天）的环孢素。在第22天处死所有大鼠并进行检查。在给药前以及给药后第7、14和21天测量血尿素氮（BUN）、血清和尿肌酐以及尿N-乙酰-s-D-氨基葡萄糖苷酶（NAG）。用光学显微镜和电子显微镜检查肾脏。所有接受100 mg/kg/天环孢素的大鼠在体重严重下降后12天内死亡。接受50或25 mg/kg/天环孢素的大鼠体重减轻，且从未恢复到给药前的体重。高剂量的环孢素导致BUN显著升高，而血清肌酐未相应升高。在实验过程中肌酐清除率的降低并不明显。虽然高剂量组的尿NAG活性增加，但升高与剂量无关。形态学改变局限于近端小管，表现为肾小管细胞空泡化和溶酶体数量增加。然而，这些改变较轻，且与环孢素剂量无关。
