Scanff P, Souidi M, Grison S, Griffiths N M, Gourmelon P
Institut de Radioprotection et de Sûreté Nucléaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidemiologie, IRSN, B.P. n 17, F-92262 Fontenay-aux-Roses CEDEX, France.
Can J Physiol Pharmacol. 2004 Feb;82(2):114-24. doi: 10.1139/y03-131.
The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed.
本研究旨在通过冲洗技术,在大鼠体内8 Gy辐射暴露3天后,研究胆汁酸肝肠循环(EHR)的急性变化。将该技术与高效液相色谱分析相结合,测定对照动物和辐照动物中主要单个胆汁酸的EHR。还在尤斯灌流小室中研究了离体回肠牛磺胆酸盐的吸收情况。同时测量了参与胆汁酸合成的主要肝酶活性。根据冲洗法测量的胆汁酸肠道含量和肠道吸收效率计算结果显示,肠道吸收减少,不同胆汁酸之间存在显著差异:牛磺胆酸盐和牛磺鼠胆酸盐的吸收减少,而疏水性更强的牛磺鹅去氧胆酸盐的吸收增加,这表明肠道被动扩散增强,而回肠主动转运可能减少。仅牛磺胆酸盐的基础肝分泌增加,这与肝脏中CYP8B1活性的显著增加一致。结果清楚地表明,在辐射诱导肠道胆汁酸吸收不良的同时,肝脏胆汁酸的合成和分泌也发生了变化。因此,提出了辐照后肝肠循环病理生理变化的当前工作模型。