Deroubaix X, Coche T, Depiereux E, Feytmans E
Unité de Biologie Quantitative, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
Am J Physiol. 1991 Feb;260(2 Pt 1):G189-96. doi: 10.1152/ajpgi.1991.260.2.G189.
A single intravenous injection of [14C]taurocholate was followed up in blood and bile of rats submitted to steady intravenous infusions of taurocholate (TC) at rates of 0.0, 0.5, 1.0, and 1.5 mumol.min-1.100 g body wt-1 for at least 30 min. The transport rate constants and the amounts of TC in different compartments were estimated by weighted least-squares adjustment of a six-compartment model to the experimental data (3 compartments for TC distribution in blood, 2 compartments for liver, and 1 compartment for sinusoidal blood space). The saturation of the TC excretion rate was reached at 0.8 mumol.min-1.100 g body wt-1. It was characterized by a decrease of both the uptake and excretion rate constants, by an increase of the ratio of the amounts of TC in the two intrahepatic compartments (H'/H), and by an intrahepatic TC concentration of approximately 2 mM. When tauroursodeoxycholate (TUDC) was infused at a rate of 0.5 mumol.min-1.100 g body wt-1 together with TC at a rate of 1.5 mumol.min-1.100 g body wt-1, the TC excretion rate increased to 1.2 mumol.min-1.100 g body wt-1, and the excretion rate constant and H'/H decreased toward control values. These results support the hypothesis that the saturation of the transport of TC is due to TC hepatotoxicity and can be reduced by TUDC. Michaelis-Menten parameters, derived from saturation curves for both uptake and excretion steps, closely matched earlier results, thus confirming the good descriptive capacity of the model.
给大鼠静脉注射单次[14C]牛磺胆酸盐后，以0.0、0.5、1.0和1.5 μmol·min-1·100 g体重-1的速率持续静脉输注牛磺胆酸盐（TC）至少30分钟，随后在其血液和胆汁中进行追踪。通过将六室模型加权最小二乘拟合到实验数据（血液中TC分布3个室、肝脏2个室、肝血窦1个室）来估算不同隔室中TC的转运速率常数和量。TC排泄速率在0.8 μmol·min-1·100 g体重-1时达到饱和。其特征为摄取和排泄速率常数均降低、两个肝内隔室中TC量的比值（H'/H）增加以及肝内TC浓度约为2 mM。当以0.5 μmol·min-1·100 g体重-1的速率输注牛磺熊去氧胆酸盐（TUDC）并同时以1.5 μmol·min-1·100 g体重-1的速率输注TC时，TC排泄速率增加至1.2 μmol·min-1·100 g体重-1，且排泄速率常数和H'/H向对照值降低。这些结果支持以下假设：TC转运的饱和是由于TC的肝毒性所致，且可被TUDC降低。从摄取和排泄步骤的饱和曲线得出的米氏参数与早期结果密切匹配，从而证实了该模型良好的描述能力。
