Borgström B, Krabisch L, Lindström M, Lillienau J
Department of Physiological Chemistry, University of Lund, Sweden.
Scand J Clin Lab Invest. 1987 Oct;47(6):543-9. doi: 10.1080/00365518709168466.
Several different methods have been applied to measure the extent of bile salt deconjugation (deamidation), if any, outside the gastro-intestinal tract of the rat. A breath test has been applied to the rat using peroral or intravenous administration of cholyl-glycine-1-14C. Results for normal rats have been compared with rats with a continuous recirculation of bile to a tail vein. Bile salts labelled with 2,4-3H in the sterol moiety and conjugated with glycine-1-14C have been infused in rats and recirculated via a bile duct tail-vein shunt. The 3H:14C ratio in the bile has been used as an indication of deconjugation. In these experiments the radioactivity pattern of the bile salts has been determined after thin-layer chromatography. Different labelled bile salts have also been infused intraperitoneally and the composition of bile secreted through bile fistulae studied. In none of these experiments, in which the gastro-intestinal content was bypassed and a return of bile salts to the liver in the physiological range ensured, was any deconjugation of glycine-conjugated bile salts observed. When the liver, however, was stressed by anaesthesia and the intraportal infusion of deoxycholyl-2,4-3H-glycine in unphysiological levels, deconjugation occurred as indicated by the appearance in bile of labelled taurine conjugates. In these rats the dose of deoxycholylglycine was clearly toxic as evidenced by partial or complete cholestasis and eventually death of the animal.
已经应用了几种不同的方法来测量大鼠胃肠道外胆汁盐去结合(脱酰胺)的程度(如果存在的话)。已通过口服或静脉注射胆酰甘氨酸 -1-14C 对大鼠进行呼气试验。将正常大鼠的结果与胆汁持续再循环至尾静脉的大鼠进行了比较。已将在甾醇部分用 2,4-3H 标记并与甘氨酸 -1-14C 结合的胆汁盐注入大鼠体内,并通过胆管 - 尾静脉分流进行再循环。胆汁中的 3H:14C 比值已被用作去结合的指标。在这些实验中,薄层色谱后测定了胆汁盐的放射性模式。还将不同标记的胆汁盐腹腔内注射,并研究了通过胆瘘分泌的胆汁成分。在这些实验中,没有一个实验(其中绕过胃肠道内容物并确保胆汁盐在生理范围内返回肝脏)观察到甘氨酸结合胆汁盐的任何去结合。然而,当肝脏受到麻醉和门静脉内注射非生理水平的脱氧胆酰 -2,4-3H-甘氨酸的应激时,如胆汁中出现标记的牛磺酸共轭物所示,发生了去结合。在这些大鼠中,脱氧胆酰甘氨酸的剂量明显有毒,表现为部分或完全胆汁淤积,最终动物死亡。