Sauer P, Rudolph G, Endele R, Senn M, Theilmann L, Otto G, Stremmel W, Stiehl A
Department of Medicine, University of Heidelberg, Germany.
Eur J Clin Invest. 1996 Nov;26(11):979-82. doi: 10.1046/j.1365-2362.1996.2290581.x.
Administration of cyclosporin A (CsA) may induce cholestasis, and this effect has been attributed to impaired hepatocellular uptake, transport, secretion and intestinal absorption of bile acids. Disturbances of the enterohepatic circulation may affect metabolism of bile acids. To test whether liver transplantation and treatment with CsA alters pool sizes or synthesis and turnover rates, we determined kinetics of primary bile acids in patients after orthotopic liver transplantation on CsA. Two male and four female patients were studied 6-20 months after transplantation. They had no overt signs of cholestasis, graft dysfunction or rejection. Kinetics of cholic acid (CA) and chenodeoxycholic acid (CDCA) were simultaneously determined after oral administration of [24-13C]-CA and [24-13C]-CDCA on the basis of isotope dilution in a single pool of bile acids. Ten healthy volunteers served as controls. After orthotopic liver transplantation, pool sizes, fractional turnover rates and synthesis rates of both primary bile acids, CA and CDCA were not significantly different from control subjects. In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids.
环孢素A(CsA)的应用可能会诱发胆汁淤积,这种效应被认为是由于肝细胞对胆汁酸的摄取、转运、分泌及肠道吸收受损所致。肠肝循环紊乱可能会影响胆汁酸的代谢。为了检测肝移植及CsA治疗是否会改变胆汁酸池大小或合成及周转率,我们测定了接受原位肝移植并使用CsA治疗的患者中初级胆汁酸的动力学。对2例男性患者和4例女性患者在移植后6 - 20个月进行了研究。他们没有胆汁淤积、移植物功能障碍或排斥反应的明显迹象。在口服[24 - 13C] - 胆酸(CA)和[24 - 13C] - 鹅去氧胆酸(CDCA)后,基于单一胆汁酸池中的同位素稀释法同时测定CA和CDCA的动力学。10名健康志愿者作为对照。原位肝移植后,两种初级胆汁酸CA和CDCA的胆汁酸池大小、分数周转率和合成率与对照受试者相比无显著差异。尽管已知CsA会干扰胆汁酸的肠肝循环,但在大多数没有胆汁淤积、移植物功能障碍或排斥反应的原位肝移植患者中,使用CsA治疗并不会干扰初级胆汁酸的动力学。