Fasano A, Budillon G, Guandalini S, Cuomo R, Parrilli G, Cangiotti A M, Morroni M, Rubino A
Dipartimento di Pediatria, 2a Facoltà di Medicina Università di Napoli, Italy.
Dig Dis Sci. 1990 Jul;35(7):801-8. doi: 10.1007/BF01536791.
To define the action of deconjugated bile acids on the small intestinal permeability in an in vitro system, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a dose-related manner the transepithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.
为了在体外系统中确定去结合胆汁酸对小肠通透性的作用，我们研究了鹅去氧胆酸和熊去氧胆酸对兔空肠和回肠黏膜中乳果糖跨膜通量速率的影响，这些黏膜已剥离肌肉层并安装在尤斯灌流小室中。在一系列实验中，还通过扫描和透射电子显微镜检查了暴露于胆汁酸或未暴露于胆汁酸的小肠段组织样本，以研究紧密连接的完整性。结果表明，鹅去氧胆酸盐从0.1 mM的浓度开始，以剂量相关的方式增强了回肠中乳果糖的跨上皮通量。鹅去氧胆酸盐（0.5 mM）和熊去氧胆酸盐（0.5 mM）均显著增加了空肠和回肠中黏膜对乳果糖的通透性；鹅去氧胆酸盐的作用也被证明是可逆的，因为在撤除后40分钟内其作用完全消失，且未导致上皮运输功能的永久性改变。最后，添加1 mM鹅去氧胆酸盐后紧密连接似乎变松散了，这表明这是胆汁酸使小肠对分子半径大于0.5 nm的化合物（如乳果糖）通透性短暂增加的主要部位。
