Whiting P H, Thomson A W, Blair J T, Simpson J G
Br J Exp Pathol. 1982 Feb;63(1):88-94.
The nephrotoxic property of cyclosporin A (Cy A) was investigated in groups of Sprague-Dawley rats given various dose regimes over a 21-day period. Impairment of glomerular filtration was clearly evidenced by elevated serum urea and creatinine levels and by reduced urea clearance rates. There were also dose-related increases in urinary N-acetyl-beta-D-glucosaminidase activity. These biochemical changes were accompanied by structural evidence of damage to the straight segment of the proximal tubule; this consisted of varying degrees of cytoplasmic vacuolation, due to dilatation of both smooth and rough endoplasmic reticulum, and, at the highest dose tested, occasional individual cell necrosis and desquamation. Ultrastructural examination revealed additional dose-related abnormalities affecting the entire length of the proximal tubule, including increased lysosome production and the formation of cytosegresomes and myeloid bodies.
在21天的时间里，对给予不同剂量环孢素A（Cy A）的几组斯普拉格-道利大鼠进行研究，以考察其肾毒性。血清尿素和肌酐水平升高以及尿素清除率降低，清楚地表明肾小球滤过功能受损。尿N-乙酰-β-D-氨基葡萄糖苷酶活性也呈剂量相关增加。这些生化变化伴随着近端小管直段损伤的结构证据；这表现为不同程度的细胞质空泡化，这是由于滑面和粗面内质网扩张所致，并且在测试的最高剂量下，偶尔会出现个别细胞坏死和脱落。超微结构检查显示，近端小管全长还存在与剂量相关的其他异常，包括溶酶体生成增加以及细胞分隔体和髓样小体的形成。
