Duncan J I, Thomson A W, Aldridge R D, Simpson J G, Whiting P H
Clin Nephrol. 1986;25 Suppl 1:S14-7.
Cyclosporine (CsA)-induced renal structural damage was investigated in rats of different strains, age and sex, and in outbred guinea pigs, given the drug orally for periods of 1 to 7 weeks. In adult male Sprague-Dawley (SD) rats, proximal straight tubular (PST) cell vacuolation and nuclear pyknosis (affecting less than 5% of tubular profiles) can consistently be demonstrated by light microscopy within a few days of commencement of treatment with 25 mg/kg. The extent of damage observed with longer term, continuous drug administration is generally more pronounced, dose-related and subject to "spontaneous" remission. Comparison of SD with DA male rats undergoing similar treatment shows that at 4 weeks, structural damage is less pronounced in the latter strain. In juvenile (LEW X DA)F1 hybrids, male animals exhibit greater susceptibility to CsA-induced nephrotoxicity than do females. This is related to differences in circulating levels of CsA in males and females. However, in adult SD rats both male and female animals show almost the same degree of tubular nephrotoxicity when given the drug at 50 mg/kg. Use of the electron microscope improves detection of early and minimal tubular cell damage: for example, in guinea pigs receiving 75 mg/kg orally for 4 days, ultrastructural changes are evident although the renal tubules are apparently unaffected when examined by light microscopy.
在不同品系、年龄和性别的大鼠以及远交豚鼠中，研究了口服环孢素（CsA）1至7周所引起的肾脏结构损伤。在成年雄性Sprague-Dawley（SD）大鼠中，给予25mg/kg药物治疗开始后的几天内，光镜检查可始终显示近端直管（PST）细胞空泡化和核固缩（影响不到5%的肾小管断面）。长期持续给药所观察到的损伤程度通常更明显，与剂量相关且会出现“自发”缓解。对接受类似治疗的SD雄性大鼠和DA雄性大鼠进行比较表明，在4周时，后一品系的结构损伤不太明显。在幼年（LEW×DA）F1杂种中，雄性动物比雌性动物对CsA诱导的肾毒性更敏感。这与雄性和雌性动物体内环孢素的循环水平差异有关。然而，在成年SD大鼠中，当给予50mg/kg药物时，雄性和雌性动物的肾小管肾毒性程度几乎相同。使用电子显微镜可提高对早期和微小肾小管细胞损伤的检测：例如，在口服75mg/kg药物4天的豚鼠中，尽管光镜检查时肾小管明显未受影响，但超微结构变化很明显。
