Whiting P H, Duncan J I, Gavin M P, Heys S D, Simpson J G, Asfar S K, Thomson A W
Br J Exp Pathol. 1985 Oct;66(5):535-42.
The effects of oral cyclosporin A (25 mg/kg/day) on renal function and structure in groups of normal, laparotomized and unilaterally nephrectomized DA rats was assessed over a 4-week period. In each group, the drug caused impairment of function, although there was evidence of improvement during the course of the study. Cyclosporin A toxicity was most marked in the nephrectomized animals, where histological examination at 4 weeks revealed extensive damage to proximal straight tubular cells. Only minimal structural damage was observed in the two other groups. Cyclosporin A concentrations in whole blood and kidney were estimated by radioimmunoassay at 4 weeks. Similar drug levels were found in normal, laparotomized and nephrectomized animals, except for an unexplained fall in blood levels in the laparotomy group. The significance of these observations is discussed in the context of current knowledge concerning the physiological effects, toxicology and pharmacology of cyclosporin A.
在为期4周的时间里，评估了口服环孢素A（25毫克/千克/天）对正常、开腹和单侧肾切除的DA大鼠肾功能和结构的影响。在每组中，该药物均导致了功能损害，尽管在研究过程中有改善的迹象。环孢素A毒性在肾切除动物中最为明显，4周时的组织学检查显示近端直管细胞受到广泛损伤。在其他两组中仅观察到最小程度的结构损伤。4周时通过放射免疫分析法估计全血和肾脏中的环孢素A浓度。在正常、开腹和肾切除动物中发现了相似的药物水平，但开腹组的血药水平出现了无法解释的下降。结合目前关于环孢素A的生理效应、毒理学和药理学的知识，讨论了这些观察结果的意义。
