胆汁中ビリルビン排泄に及ぼすウルソデオキシコール酸の影響 ： 胆汁酸抱合の意義

Abstract

The biliary excretion of bilirubin was studied in normal Sprague-Dawley rats and mutant jaundiced rats (Eizai hyperbilirubinuria rat, EHBR) under the continuous intravenous infusion of free ursodeoxycholate, tauroursodeoxycholate, glycoursodeoxycholate and ursodeoxycholate-glucuronide. Continuous infusion of free ursodeoxycholate at a rate of 0.6 μmol/min/100 g B. W. promoted the biliary excretion of bilirubin in normal rats. However, it suppressed the biliary excretion of bilirubin in EHBR and β-alanine-fed rats, which were associated with defective conjugation of ursodeoxycholate with taurine. When the infusion rate was increased to 1.2 μmol/min/100 g B. W., free ursodeoxycholate turned out to suppress the biliary excreiton of bilirubin in normal rats. However, when taurine or glycine was infused simultaneously, the biliary excretion of bilirubin was not suppressed, but was augmented remarkably. In addition, taurine was more effective than glycine in the promotion of the biliary excretion of bilirubin. Continuous infusion of tauroursodeoxycholate and glycoursodeoxycholate always increased the biliary excretion of bilirubin in normal rats, EHBR and β-alanine-fed rats. On the other hand, ursodeoxycholate-glucuronide extremely suppressed the biliary excretion of bilirubin even in normal rats at lower infusion rate, 0.3 μmol/min/100 g B. W.. These results indicate that bile acid conjugation, especially conjugation with taurine, plays a very important role in the biliary excretion of bilirubin.