Rotolo F S, Branum G D, Bowers B A, Meyers W C
Am J Surg. 1986 Jan;151(1):35-40. doi: 10.1016/0002-9610(86)90008-5.
Short-term effects of cyclosporine were studied in the isolated perfused rat liver model. Bile flow was inhibited by cyclosporine in 2 mg/kg and 20 mg/kg doses but not by a 0.2 mg/kg dose. Cholestasis was accompanied by a decrease in bile acid secretion, indicating an inhibitory effect on the bile acid-dependent fraction of bile flow. Perfusate bilirubin levels increased threefold in rat livers given 20 mg/kg of cyclosporine, but did not change in control animals. Alkaline phosphatase and transaminase levels did not differ from those of control animals. The isolated perfused rat liver was able to excrete cyclosporine, as demonstrated by a continual decrease in perfusate cyclosporine levels. No light microscopic evidence of cholestasis or hepatocellular damage was demonstrated on histologic staining. Our model appears to be a good one for the study of altered hepatic physiologic characteristics caused by administration of cyclosporine.
在离体灌注大鼠肝脏模型中研究了环孢素的短期效应。2mg/kg和20mg/kg剂量的环孢素可抑制胆汁流量，但0.2mg/kg剂量则无此作用。胆汁淤积伴随着胆汁酸分泌减少，表明对胆汁流量中胆汁酸依赖性部分有抑制作用。给予20mg/kg环孢素的大鼠肝脏中灌注液胆红素水平增加了三倍，但对照动物中未发生变化。碱性磷酸酶和转氨酶水平与对照动物无差异。如灌注液中环孢素水平持续下降所示，离体灌注大鼠肝脏能够排泄环孢素。组织学染色未显示胆汁淤积或肝细胞损伤的光镜证据。我们的模型似乎是研究环孢素给药引起的肝脏生理特性改变的良好模型。
