McAuley F T, Simpson J G, Thomson A W, Whiting P H
Toxicol Lett. 1986 Jul-Aug;32(1-2):163-9. doi: 10.1016/0378-4274(86)90063-9.
The acute nephrotoxic properties of cyclosporin A (CsA) were investigated in normotensive, adult male Sprague-Dawley rats. Animals received either 50 or 100 mg CsA/kg by gastric intubation for 7 days. Within 24 h, significant increases in urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma GT) activity were observed at both doses of CsA. Renal function abnormalities, however, were not apparent until 2 days (100 mg/kg) or 7 days (50 mg/kg). Progressive increases in enzymuria were evident in both groups between 1 and 4 days, at which later time proximal straight tubular cell damage was first observed. The data obtained using this model clearly demonstrate that enzymuria provides a sensitive index of acute CsA-induced renal cell damage and that enzymuria precedes detectable renal functional and structural abnormalities.
在正常血压的成年雄性Sprague-Dawley大鼠中研究了环孢素A（CsA）的急性肾毒性特性。动物通过胃内插管接受50或100mg CsA/kg，持续7天。在24小时内，两种剂量的CsA均观察到尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）和γ-谷氨酰转肽酶（γGT）活性显著增加。然而，直到2天（100mg/kg）或7天（50mg/kg）才出现明显的肾功能异常。两组在1至4天期间酶尿均逐渐增加，在稍后的这个时间首次观察到近端直管细胞损伤。使用该模型获得的数据清楚地表明，酶尿是急性CsA诱导的肾细胞损伤的敏感指标，并且酶尿先于可检测到的肾功能和结构异常出现。
