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血清与胆汁中胆汁酸的关系作为恒河猴鹅去氧胆酸和熊去氧胆酸诱导肝毒性的指标

Relationship between serum and biliary bile acids as an indicator of chenodeoxycholic and ursodeoxycholic acid-induced hepatotoxicity in the rhesus monkey.

作者信息

Bazzoli F, Roda A, Fromm H, Sarva R P, Roda E, Barbara L

出版信息

Dig Dis Sci. 1982 May;27(5):417-24. doi: 10.1007/BF01295650.

Abstract

The relationship between serum and biliary concentrations of bile acids was studied in 20 rhesus monkeys which developed hepatotoxicity after six months of treatment with 40 and 120 mg/kg/day doses of chenodeoxycholic (cheno) and ursodeoxycholic (urso) acids, respectively. During the treatment, lithocholate--all of which was unsulfated--increased several-fold both in serum and in bile. There was a significant correlation between serum and biliary concentrations of lithocholate. Similarly close correlations existed between the serum and biliary concentrations of the conjugates of cheno and urso which increased during treatment with the respective bile acids. The serum levels of cholate and deoxycholate remained normal, although their concentrations in bile decreased considerably during treatment with cheno and urso, respectively. Further studies have to establish whether serum determinations of lithocholate can also be used in man to study the role of this bile acid in the liver function abnormalities which develop in some patients treated with cheno or urso and/or whether measurement of serum cheno or urso could be useful for the monitoring of patient compliance with the respective bile acid treatment.

摘要

在20只恒河猴中研究了血清胆汁酸浓度与胆汁胆汁酸浓度之间的关系,这些恒河猴在分别用40毫克/千克/天和120毫克/千克/天剂量的鹅去氧胆酸(鹅去氧胆酸)和熊去氧胆酸(熊去氧胆酸)治疗6个月后出现了肝毒性。在治疗期间,石胆酸盐(所有这些都是未硫酸化的)在血清和胆汁中均增加了几倍。血清石胆酸盐浓度与胆汁石胆酸盐浓度之间存在显著相关性。同样,在分别用相应胆汁酸治疗期间增加的鹅去氧胆酸和熊去氧胆酸的结合物的血清浓度与胆汁浓度之间也存在密切相关性。胆酸盐和脱氧胆酸盐的血清水平保持正常,尽管它们在胆汁中的浓度在分别用鹅去氧胆酸和熊去氧胆酸治疗期间显著降低。进一步的研究必须确定血清石胆酸盐的测定是否也可用于人类,以研究这种胆汁酸在一些接受鹅去氧胆酸或熊去氧胆酸治疗的患者中出现的肝功能异常中的作用,以及/或者血清鹅去氧胆酸或熊去氧胆酸的测量是否有助于监测患者对相应胆汁酸治疗的依从性。

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