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仓鼠体内同时给予鹅去氧胆酸和熊去氧胆酸的代谢比较研究。

Comparative studies of metabolism of simultaneously administered chenodeoxycholic acid and ursodeoxycholic acid in hamsters.

作者信息

Kihira K, Yamauchi T, Kuramoto T, Une M, Yoshii M, Hoshita T

机构信息

Department of Pharmaceutical Services, Hiroshima University Hospital, Japan.

出版信息

Steroids. 1994 Jul;59(7):431-5. doi: 10.1016/0039-128x(94)90012-4.

Abstract

We present the comparative studies of metabolism of chenodeoxycholic acid and ursodeoxycholic acid and their taurine conjugates in the liver and fecal culture from hamsters. When [24-14C]chenodeoxycholic acid and [11,12-3H]ursodeoxycholic acid were simultaneously instilled into the jujunal loop of bile fistula hamsters, both bile acids administered were recovered mainly as their conjugates with taurine and glycine in the fistula bile. The recovery of chenodeoxycholic acid was slightly but significantly higher than that of ursodeoxycholic acid. Chenodeoxycholic acid was more efficiently conjugated with glycine than ursodeoxycholic acid. The glycine/taurine ratio in the biliary chenodeoxycholic acid was 1.9, and that in ursodeoxycholic acid was 1.6. In addition, as much as 6.2% of ursodeoxycholic acid was excreted as the unconjugated form; on the other hand only 2.4% of unconjugated chenodeoxycholic acid was excreted. When [24-14C]chenodeoxycholyltaurine and [11,12-3H]ursodeoxycholyltaurine were simultaneously administered into the ileum loop of bile fistula hamsters, both bile salts were absorbed and secreted efficiently into the bile at the same rate. These results indicate that slightly lower recovery of ursodeoxycholic acid in the bile could be due to the less effective conjugation of ursodeoxycholic acid than chenodeoxycholic acid in the liver. Deconjugation by fecal culture from a hamster proceeded more rapidly in chenodeoxycholyltaurine than ursodeoxycholyltaurine. 7-Dehyroxylation to form lithocholic acid by fecal culture was also faster in chenodeoxycholic acid than ursodeoxycholic acid. The formation of 7-oxolithocholic acid from ursodeoxycholic acid was lesser than from chenodeoxycholic acid. In summary, bacterial deconjugation followed by 7-dehydroxylation to form lithocholic acid seems to be achieved more efficiently with chenodeoxycholic acid than ursodeoxycholic acid.

摘要

我们展示了仓鼠肝脏和粪便培养物中鹅去氧胆酸和熊去氧胆酸及其牛磺酸共轭物的代谢比较研究。当将[24-¹⁴C]鹅去氧胆酸和[11,12-³H]熊去氧胆酸同时注入胆瘘仓鼠的空肠肠袢时,两种给药的胆汁酸在瘘管胆汁中主要以它们与牛磺酸和甘氨酸的共轭物形式被回收。鹅去氧胆酸的回收率略高于熊去氧胆酸,但差异显著。与熊去氧胆酸相比,鹅去氧胆酸与甘氨酸的共轭更有效。胆汁中鹅去氧胆酸的甘氨酸/牛磺酸比值为1.9,熊去氧胆酸的该比值为1.6。此外,高达6.2%的熊去氧胆酸以未共轭形式排泄;另一方面,仅2.4%的未共轭鹅去氧胆酸被排泄。当将[24-¹⁴C]鹅去氧胆酰牛磺酸和[11,12-³H]熊去氧胆酰牛磺酸同时注入胆瘘仓鼠的回肠肠袢时,两种胆盐以相同速率被有效吸收并分泌到胆汁中。这些结果表明,熊去氧胆酸在胆汁中回收率略低可能是由于其在肝脏中与鹅去氧胆酸相比共轭效果较差。仓鼠粪便培养物对鹅去氧胆酰牛磺酸的去共轭作用比熊去氧胆酰牛磺酸进行得更快。粪便培养物将鹅去氧胆酸7-脱羟基形成石胆酸的速度也比熊去氧胆酸快。由熊去氧胆酸形成鹅去氧胆酸的7-氧石胆酸比由鹅去氧胆酸形成的要少。总之,细菌去共轭作用随后7-脱羟基形成石胆酸似乎在鹅去氧胆酸中比在熊去氧胆酸中更有效地实现。

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