Thliveris J A, Yatscoff R W, Lukowski M P, Copeland K R
Health Sciences Clinical Research Centre, University of Manitoba, Winnipeg, Canada.
Clin Biochem. 1991 Feb;24(1):93-5. doi: 10.1016/0009-9120(91)90357-k.
Cyclosporine A (CsA) represents one of the more important therapeutic advances in the field of kidney transplantation. However, its effectiveness is limited by serious side effects, most notably nephrotoxicity. Investigation of the mechanisms of CsA-induced renal dysfunction has been hampered by the lack of a suitable experimental model. The majority of studies using the rodent have failed to exhibit all of the structural changes seen in chronic CsA-induced nephrotoxicity reported in man, using pharmacologic doses administered orally, subcutaneously, or intravenously. More recently, studies using the rabbit as an experimental model have demonstrated leucocyte infiltration, tubular atrophy, interstitial fibrosis, and arteriolopathy after therapeutic doses of CsA over 30 days. These changes are similar to those seen in chronic CsA-induced nephrotoxicity in man.
环孢素A（CsA）是肾移植领域较为重要的治疗进展之一。然而，其有效性受到严重副作用的限制，最显著的是肾毒性。由于缺乏合适的实验模型，对CsA诱导的肾功能障碍机制的研究受到了阻碍。大多数使用啮齿动物的研究未能呈现出人类慢性CsA诱导肾毒性中所观察到的所有结构变化，这些研究采用口服、皮下或静脉注射药理剂量的CsA。最近，以兔子作为实验模型的研究表明，给予治疗剂量的CsA超过30天后，会出现白细胞浸润、肾小管萎缩、间质纤维化和小动脉病变。这些变化与人类慢性CsA诱导肾毒性中所观察到的变化相似。
