A study on the urinary excretion of bileacids and organic anions in bileduct-ligated rats

在胆管完全梗阻的患者中，胆汁酸消除的唯一途径是尿。然而，尿中亲胆化合物与胆管梗阻的关系尚不清楚。因此，比较胆管结扎后3天大鼠尿液中胆汁酸和有机阴离子、阳离子的排泄情况。膀胱插管后，静脉注射放射性标记物质，每隔1 ~ 2 h采集尿样，持续4 ~ 6 h，计数放射性。尿中牛磺胆酸盐和胆酸盐的排泄量（6 h内累积剂量%）相似（分别为19.3%和16.8%）。尿排泄牛磺酸去氧胆酸盐、石胆酸盐和硫酸牛磺酸石胆酸盐效果较差（分别为12.7%、9.8%和2.1%）。与对照组（5.5%）相比，胆管结扎大鼠尿中普伐他汀的排泄量（4 h累积剂量%）显著增加（86%）。替莫普利与胆管结扎大鼠有相似但不太显著的差异（分别为51%和22%）。胆管结扎大鼠红霉素尿排泄量（4 h累积剂量%）较对照组（1.9%）显著增加（49%）。在胆管结扎大鼠和对照大鼠中，vinbiastine的差异不太显著（分别为18%和7.4%）。这些结果表明，即使在胆管完全阻塞的情况下，未结合的胆汁酸也会被肝脏吸收并在进一步的生物转化后排泄到血液中。虽然硫酸胆汁酸是梗阻性黄疸患者尿液中的主要胆汁酸，但单羟基胆汁酸被认为即使与牛磺酸和硫酸结合也不能有效地排泄到尿液中。胆管结扎大鼠尿液排泄对有机阴离子和阳离子的消除也有补偿作用，但不同化合物对有机阴离子和阳离子的补偿程度不同，可能与这些化合物在胆汁淤积时肾脏转运蛋白的改变有关。少

In patients with complete bile duct obstruction, the only pathway of bile acid elimination is by the urine. However urinary excretion of cholephilic compounds with bile duct obstruction has not been clarified. Therefore, the urinary excretion of bile acids and organic anions and cations was compared in bile duct-ligated rats for 3 days. After urinary bladder cannulation, radiolabeled materials were intravenously injected, and urine samples were collected every 1-2 hrs for 4-6 h and radioactivity was counted. Urinary excretion (cumulative %dose during 6 h) of taurocholate and cholate was similar (19.3% and 16.8%). Urinary excretion of tauroursodeoxycholate, lithocholate and taurolithocholate-sulfate was less effective (12.7 %, 9.8 % and 2.1%, respectively). Urinary excretion (cumulative %dose during 4 h) of pravastatin was markedly increased in bile duct-ligated rats (86%) compared with control rats (5.5%). Similar but less prominent differences were observed with temocapril (51% and 22 … More % in bile duct-ligated and control rats, respectively). Urinary excretion (cumulative %dose during 4 h) of erythromycin was markedly increased in bile duct-ligated rats (49%) compared with control rats (1.9%). Less prominent differences were observed with vinbiastine (18% and 7.4% in bile duct-ligated and control rats, respectively). These results indicate that unconjugated bile acids were taken up by the liver and excreted into blood after further biotransformation even under complete bile duct obstruction. Although bile acid sulfates are major bile acids in the urine of patients with obstructive jaundice, monohydroxylated bile acids are considered to be not so effectively excreted into the urine even with conjugation with taurine and sulfate in rats. The elimination of organic anions and cations are also compensated for by the urinary excretion in bile duct-ligated rats, the extent of the compensation was different among compounds, possibly due to the changes of renal transporter for these compounds in cholestasis. Less