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

胆管结扎大鼠尿中胆汁酸和有机阴离子排泄的研究

• 批准号: 14570510
• 负责人: TAKIKAWA Hajime
• 金额: $ 1.98万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570510/
• 关键词: bile acid; organic anion; bile duct ligation; janudice; urinary excretion; 閉塞性黄疸

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

在完全性胆管梗阻的患者中，胆汁酸的唯一排泄途径是通过尿液。然而，胆道梗阻时的嗜胆化合物尿排泄尚未明确。因此，比较了胆管结扎大鼠3天的胆汁酸和有机阴离子和阳离子的尿排泄。膀胱插管后，静脉内注射放射性标记材料，每1-2小时采集一次尿样，持续4-6小时，并对放射性进行计数。牛磺胆酸盐和胆酸盐的尿排泄（6 h内累积%剂量）相似（19.3%和16.8%）。牛磺熊去氧胆酸盐、石胆酸盐和牛磺石胆酸盐硫酸盐的尿排泄效果较差（分别为12.7%、9.8%和2.1%）。与对照组大鼠（5.5%）相比，胆管结扎大鼠（86%）中普伐他汀的尿排泄（4 h内累积%剂量）显著增加。与替莫普利相似，但差异不太显著（51%和22 ...更多信息 %，分别在胆管结扎和对照大鼠中）。与对照组大鼠（1.9%）相比，胆管结扎大鼠（49%）的红霉素尿排泄（4 h内累积%剂量）显著增加。在长春比斯汀组中观察到的差异不太显著（胆管结扎大鼠和对照大鼠中分别为18%和7.4%）。这些结果表明，即使在完全胆管阻塞的情况下，未结合胆汁酸也被肝脏吸收，并在进一步生物转化后排泄到血液中。虽然胆汁酸硫酸盐是阻塞性黄疸患者尿液中的主要胆汁酸，但认为单羟基化胆汁酸即使与牛磺酸和硫酸盐结合，也不能有效地排泄到尿液中。胆汁淤积时，有机阴、阳离子的排泄也可通过尿排泄得到补偿，补偿程度因化合物而异，可能与胆汁淤积时肾脏转运体的变化有关。少

项目成果

Takeuchi A, Sano N, Takikawa H: "Inhibition of ileal bile acid absorption by colestimide"Journal of Gastroenterology and Hepatology. 18. 548-553 (2003)

Takeuchi A、Sano N、Takikawa H：“考来司胺对回肠胆汁酸吸收的抑制”胃肠病学和肝病学杂志。

Takikawa H, et al.: "Biliary excretion of taurolithocholate-sulfate and temocaprilat in cholestatic rats induced by bile duct-ligation and ethinylestradiol"Hepatology Research. vol.24. 136-140 (2002)

Takikawa H 等人：“胆管结扎和炔雌醇诱导胆汁淤积大鼠中牛磺石胆酸盐硫酸盐和替莫普利拉的胆汁排泄”肝病学研究。

Takada Y, et al.: "Comparison of urinary excretion of pravastatin and temocapril in bile duct ligated rats and Eisai hyperbilirubinemic rats (EHBR)"J Hep-Bil-Panc Surg. (in press).

Takada Y 等人：“胆管结扎大鼠和卫材高胆红素血症大鼠 (EHBR) 中普伐他汀和替莫普利尿排泄的比较”J Hep-Bil-Panc Surg。

Takikawa H: "Hepatobiliary transport of bile acids and organic anions"Journal of Hepato-Biliary-Pancreatic Surgery. vol.9. 443-447 (2002)

泷川 H：“胆汁酸和有机阴离子的肝胆转运”肝胆胰外科杂志。

Hanawa N, Sano N, Takikawa H: "Biliary excretion of azelnidipine, a calcium antagonist, in rats"Journal of Gastroenterology and Hepatology. 19. 413-417 (2004)

Hanawa N、Sano N、Takikawa H：“钙拮抗剂阿折地平在大鼠体内的胆汁排泄”胃肠病学和肝脏病学杂志。