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艾司西酞普兰高胆红素血症大鼠(EHBR)中石胆酸-3-硫酸盐的胆汁排泄机制。

Mechanisms of biliary excretion of lithocholate-3-sulfate in Eisai hyperbilirubinemic rats (EHBR).

作者信息

Takikawa H, Nishikawa K, Sano N, Yamanaka M, Horie T

机构信息

Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.

出版信息

Dig Dis Sci. 1995 Aug;40(8):1792-7. doi: 10.1007/BF02212704.

DOI:10.1007/BF02212704
PMID:7648982
Abstract

Biliary excretion of lithocholate-3-sulfate is markedly impaired in EHBR. To examine the mechanism of biliary lithocholate-3-sulfate excretion in EHBR, the effects of colchicine treatment, a vesicular transport inhibitor, and infusion of taurocholate and organic anions were studied in EHBR and Sprague-Dawley rats. Colchicine treatment and taurocholate infusion had no effect of biliary lithocholate-3-sulfate excretion in EHBR, suggesting that biliary lithocholate-3-sulfate excretion is not mediated by the vesicular transport or by the bile acid excretory pathway. In control Sprague-Dawley rats, both sulfobromophthalein and dibromosulfophthalein infusion inhibited biliary lithocholate-3-sulfate excretion. In contrast, in EHBR dibromosulfophthalein infusion inhibited biliary lithocholate-3-sulfate excretion but BSP infusion did not. Indocyanine green and pravastatin infusion did not affect biliary lithocholate-3-sulfate excretion but pravastatin infusion had no effect in EHBR. These findings indicate that, whether physiologically important or not, two of more excretory pathways for organic anions exist at the canalicular membrane other than the ATP-dependent one.

摘要

在EHBR中,石胆酸-3-硫酸盐的胆汁排泄明显受损。为了研究EHBR中胆汁石胆酸-3-硫酸盐排泄的机制,在EHBR和Sprague-Dawley大鼠中研究了秋水仙碱治疗(一种囊泡转运抑制剂)、牛磺胆酸盐输注和有机阴离子输注的影响。秋水仙碱治疗和牛磺胆酸盐输注对EHBR中胆汁石胆酸-3-硫酸盐的排泄没有影响,这表明胆汁石胆酸-3-硫酸盐的排泄不是由囊泡转运或胆汁酸排泄途径介导的。在对照Sprague-Dawley大鼠中,磺溴酞钠和二溴磺酞钠输注均抑制胆汁石胆酸-3-硫酸盐的排泄。相比之下,在EHBR中,二溴磺酞钠输注抑制胆汁石胆酸-3-硫酸盐的排泄,但磺溴酞钠输注则无此作用。吲哚菁绿和普伐他汀输注不影响胆汁石胆酸-3-硫酸盐的排泄,但普伐他汀输注对EHBR无影响。这些发现表明,无论生理上是否重要,除了ATP依赖性途径外,在胆小管膜上还存在两种或更多种有机阴离子排泄途径。

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引用本文的文献

1
Enhanced biliary excretion of lithocholate-3-sulfate by ursodeoxycholate-3,7-disulfate infusion in Eisai hyperbilirubinemic rat (EHBR).在艾塞那(Eisai)高胆红素血症大鼠(EHBR)中,通过输注熊去氧胆酸-3,7-二硫酸盐增强石胆酸-3-硫酸盐的胆汁排泄。
Dig Dis Sci. 1998 Jan;43(1):188-92. doi: 10.1023/a:1018809028425.
2
Effects of organic anions and bile acid conjugates on biliary excretion of pravastatin in the rat.有机阴离子和胆汁酸结合物对大鼠普伐他汀胆汁排泄的影响。
Pharm Res. 1998 Jan;15(1):72-6. doi: 10.1023/a:1011900820409.

本文引用的文献

1
Kinetic analysis of hepatobiliary transport of organic anions in Eisai hyperbilirubinemic mutant rats.卫材高胆红素血症突变大鼠有机阴离子肝胆转运的动力学分析
J Pharmacol Exp Ther. 1993 Jun;265(3):1301-12.
2
Effects of organic anions and bile acids on biliary lipid excretion in hyperbilirubinemic mutant Sprague-Dawley rats.有机阴离子和胆汁酸对高胆红素血症突变型Sprague-Dawley大鼠胆汁脂质排泄的影响。
J Hepatol. 1993 Feb;17(2):247-52. doi: 10.1016/s0168-8278(05)80046-7.
3
Estradiol-17 beta-glucuronide-induced cholestasis. Effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate.
17β-雌二醇葡萄糖醛酸苷诱导的胆汁淤积。熊去氧胆酸-3-O-葡萄糖醛酸苷和3,7-二硫酸盐的作用。
J Hepatol. 1993 Feb;17(2):241-6. doi: 10.1016/s0168-8278(05)80045-5.
4
Lithocholate-3-O-glucuronide-induced cholestasis. A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates.石胆酸 -3-O-葡萄糖醛酸苷诱导的胆汁淤积。对先天性高胆红素血症大鼠的研究及熊去氧胆酸共轭物的作用
Dig Dis Sci. 1993 Aug;38(8):1543-8. doi: 10.1007/BF01308618.
5
Multiple transport systems for organic anions across the bile canalicular membrane.多种有机阴离子跨胆小管膜转运系统。
J Pharmacol Exp Ther. 1994 Jan;268(1):65-73.
6
Hepatocellular transport of bile acids. Evidence for distinct subcellular localizations of electrogenic and ATP-dependent taurocholate transport in rat hepatocytes.胆汁酸的肝细胞转运。大鼠肝细胞中电生性和ATP依赖性牛磺胆酸盐转运的不同亚细胞定位的证据。
J Biol Chem. 1994 Feb 18;269(7):5179-86.
7
Intracellular bile acid transport in rat liver as visualized by electron microscope autoradiography using a bile acid analogue.使用胆汁酸类似物通过电子显微镜放射自显影观察大鼠肝脏中的细胞内胆汁酸转运。
Am J Physiol. 1983 Nov;245(5 Pt 1):G681-9. doi: 10.1152/ajpgi.1983.245.5.G681.
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Effect of colchicine and S,S,S-tributyl phosphorotrithioate (DEF) on the biliary excretion of sucrose, mannitol and horseradish peroxidase in the rat.秋水仙碱和三硫磷(DEF)对大鼠胆汁中蔗糖、甘露醇和辣根过氧化物酶排泄的影响。
Biochem Pharmacol. 1983 Jan 1;32(1):85-90. doi: 10.1016/0006-2952(83)90657-3.
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Shared and separate pathways for biliary excretion of bilirubin and BSP in rats.大鼠胆红素和磺溴酞钠经胆汁排泄的共同和独立途径
Am J Physiol. 1973 Jul;225(1):192-200. doi: 10.1152/ajplegacy.1973.225.1.192.
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Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport.肝脏阴离子转运缺陷导致突变大鼠遗传性慢性结合胆红素血症。
Hepatology. 1985 Jul-Aug;5(4):573-9. doi: 10.1002/hep.1840050408.