Sutherland F R, Preshaw R M, Shaffer E A
Faculty of Medicine, University of Calgary, Alta., Canada.
Can J Physiol Pharmacol. 1990 Jan;68(1):136-8. doi: 10.1139/y90-021.
Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg.kg-1.d-1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 mumols.kg-1.min-1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg.kg-1,d-1, respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose-related choleresis without any change in bile salt secretion.
据报道，环孢素A可导致胆汁淤积，但急性实验中使用的麻醉和手术使证据变得复杂。为了更好地研究环孢素对肝脏的影响，通过慢性十二指肠瘘管将胆总管插管，直接测量了三只胆囊切除狗的胆汁输出量。术后1个月进行对照研究。然后连续1周给予口服剂量为5、15和50mg·kg-1·d-1的环孢素。在每个研究期间，对禁食、清醒的动物测量两次5小时的胆汁输出量：3小时以建立基础条件，随后以1和2μmol·kg-1·min-1的剂量输注牛磺胆酸盐2小时。在基础条件下，胆汁流量随环孢素的每一个剂量增加，分别比环孢素5、15和50mg·kg-1·d-1的对照增加63%、127%和179%。在牛磺胆酸刺激期间，胆汁流量也有类似增加。环孢素对胆盐或胆红素分泌没有影响。在这个与其他胆汁淤积原因隔离的慢性狗模型中，环孢素不会诱导胆汁淤积，而是引起剂量相关的胆汁分泌增多，且胆盐分泌没有任何变化。
