Sánchez Pozzi E J, Mottino A D, Sisti A, Roma M G
Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET-U.N.R., Rosario, Argentina.
Life Sci. 1995;57(10):973-81. doi: 10.1016/0024-3205(95)02032-e.
The effects of ursodeoxycholate and its taurine conjugate on biliary Tm of bilirubin were evaluated in rats. Ursodeoxycholate was administered at four different doses (4, 8, 12 or 16 mumol per 100 g body wt i.v., followed by an i.v. infusion of 0.3, 0.6, 0.9 or 1.2 mumol/min per 100 g body wt, respectively), whereas tauroursodeoxycholate was administered only at the maximal dose. A dose-dependent diminution of bilirubin Tm was observed during ursodeoxycholate administration, which ranged from no effect at the lowest dose to a virtual excretory blockage at the highest dose. This was associated with an increase in bilirubin concentrations in both plasma and liver as well as in the fractional amount of conjugated pigment in both sites, suggesting an impairment of bilirubin transfer at the canalicular level. Incomplete taurine conjugation of ursodeoxycholate well correlated with these effects. Unlike ursodeoxycholate, tauroursodeoxycholate had no inhibitory effect on bilirubin Tm, although a slight inhibition of bilirubin uptake and bilirubin conjugation became apparent. Taken together, these results suggest that ursodeoxycholate interferes with the hepatobiliary transport of bilirubin by impairing its transfer at the canalicular level and that incomplete taurine conjugation appears to be a key factor determining this effect.
在大鼠中评估了熊去氧胆酸及其牛磺酸共轭物对胆红素胆汁转运最大值（Tm）的影响。熊去氧胆酸以四种不同剂量给药（静脉注射，每100克体重分别为4、8、12或16微摩尔，随后分别以每100克体重每分钟0.3、0.6、0.9或1.2微摩尔的速度静脉输注），而牛磺熊去氧胆酸仅以最大剂量给药。在给予熊去氧胆酸期间观察到胆红素Tm呈剂量依赖性降低，从最低剂量时无影响到最高剂量时几乎完全排泄受阻。这与血浆和肝脏中胆红素浓度的增加以及两个部位结合胆红素分数的增加相关，提示在胆小管水平胆红素转运受损。熊去氧胆酸的牛磺酸结合不完全与这些效应密切相关。与熊去氧胆酸不同，牛磺熊去氧胆酸对胆红素Tm没有抑制作用，尽管对胆红素摄取和胆红素结合有轻微抑制作用。综上所述，这些结果表明熊去氧胆酸通过损害其在胆小管水平的转运来干扰胆红素的肝胆转运，并且不完全的牛磺酸结合似乎是决定这种效应的关键因素。
