Sutherland F R, Preshaw R M, Shaffer E A
GI Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Transplantation. 1993 Feb;55(2):237-42. doi: 10.1097/00007890-199302000-00001.
Following liver transplantation bile formation may be influenced by hepatic denervation and cyclosporine therapy. To better establish any effect of liver transplantation on bile secretion, 6 mongrel dogs were studied: 3 underwent liver denervation by a modified autotransplantation procedure and insertion of a Thomas cannula to create a chronic duodenal fistula; 3 others had cholecystectomy and the duodenal cannula placement without manipulating the liver. One month after surgery, two control studies were done, one week apart. Then oral cyclosporine was given in doses of 5, 15, and 50 mg/kg/day for consecutive 1-week periods each. Twice on each cyclosporine regimen, after 4 and 7 days of therapy, the common duct was cannulated and bile collected for 5 h; animals were awake and fasted. The first 3 h of bile collection established basal conditions; flow was then stimulated with consecutive hour-long taurocholate infusions at 1 and 2 mumol/kg/min. In all dogs, bile flow increased as the cyclosporine dose increased, under both basal and bile salt-stimulated conditions. The increased flow primarily resulted from increased bile salt-independent flow. Cyclosporine had no effect on bile salt, bilirubin, or cholesterol secretion. Phospholipid secretion, however, decreased significantly in a dose-related manner with increasing cyclosporine in the dogs with autotransplanted livers, but not in the nontransplanted dogs. This decrease in phospholipid secretion resulted in a significant increase in the calculated cholesterol saturation of bile. Thus, cyclosporine administered orally is not cholestatic but rather increases bile flow independent of any change in bile salt secretion. Cyclosporine reduced phospholipid secretion in autotransplanted dogs, possibly related to denervation of the liver. The resultant change in biliary composition may pose a risk factor for gallstone formation.
肝移植后，胆汁形成可能会受到肝去神经支配和环孢素治疗的影响。为了更好地确定肝移植对胆汁分泌的任何影响，对6只杂种犬进行了研究：3只通过改良的自体移植手术进行肝去神经支配，并插入托马斯套管以形成慢性十二指肠瘘；另外3只进行了胆囊切除术并放置十二指肠套管，而未对肝脏进行操作。手术后1个月，进行了两项对照研究，间隔1周。然后连续1周每天以5、15和50 mg/kg的剂量口服环孢素。在每种环孢素治疗方案下，治疗4天和7天后，两次将胆总管插管并收集胆汁5小时；动物清醒且禁食。胆汁收集的前3小时确定基础条件；然后以1和2 μmol/kg/min的剂量连续1小时输注牛磺胆酸盐刺激胆汁流动。在所有犬中，在基础和胆盐刺激条件下，胆汁流量均随环孢素剂量的增加而增加。流量增加主要是由于不依赖胆盐的流量增加。环孢素对胆盐、胆红素或胆固醇分泌没有影响。然而，在进行自体肝移植的犬中，磷脂分泌随着环孢素剂量的增加而以剂量相关的方式显著降低，但在未进行移植的犬中则没有。磷脂分泌的这种减少导致胆汁中计算出的胆固醇饱和度显著增加。因此，口服环孢素不会引起胆汁淤积，而是会增加胆汁流量，且与胆盐分泌的任何变化无关。环孢素降低了自体移植犬的磷脂分泌，这可能与肝脏去神经支配有关。胆汁成分的这种变化可能构成胆结石形成的危险因素。
