Breuer N F, Rampton D S, Tammar A, Murphy G M, Dowling R H
Gastroenterology. 1983 May;84(5 Pt 1):969-77.
A single-pass perfusion system was used in conscious restrained rats to measure changes in water and electrolyte transport and in protein and deoxyribonucleic acid output after perfusing 5-15-mM solutions of sulfated or nonsulfated bile acids through the colon. Perfusion with 5 mM nonsulfated deoxycholic acid or chenodeoxycholic acid changed net water and sodium absorption to net secretion, provoked marked increases in protein and DNA output into the perfusion effluent, and caused microscopic mucosal damage. In contrast, perfusion with 5 and 15 mM sulfated deoxycholic acid or with 5 mM sulfated chenodeoxycholic acid had no effect on water and electrolyte transport and caused only modest changes in protein and DNA output. To see whether or not sulfated bile acid could prevent the effect of its nonsulfated parent compound on colonic structure and function, perfusion with a mixture of 5 mM nonsulfated and 10 mM sulfated deoxycholic acid was performed. This produced net secretion of water and sodium together with less marked increases of protein and deoxyribonucleic acid output and less pronounced microscopic mucosal damage than was seen after 5 mM nonsulfated deoxycholic acid alone. Finally, 5 mM nonsulfated cholic acid had no effect on water or sodium transport, but 5 mM sulfated cholic acid, with one alpha-hydroxyl group masked and two alpha-hydroxyl groups "exposed," reduced water transport. These results suggest that sulfation prevents the cathartic effect of alpha-dihydroxyl bile acids in the colon.
在清醒的束缚大鼠中使用单通道灌注系统,通过向结肠灌注5-15 mM的硫酸化或非硫酸化胆汁酸溶液,来测量水和电解质转运以及蛋白质和脱氧核糖核酸输出的变化。用5 mM非硫酸化脱氧胆酸或鹅去氧胆酸灌注会使净水和钠吸收转变为净分泌,导致灌注流出物中的蛋白质和DNA输出显著增加,并引起微观黏膜损伤。相比之下,用5 mM和15 mM硫酸化脱氧胆酸或5 mM硫酸化鹅去氧胆酸灌注对水和电解质转运没有影响,仅使蛋白质和DNA输出发生适度变化。为了观察硫酸化胆汁酸是否能预防其非硫酸化母体化合物对结肠结构和功能的影响,进行了用5 mM非硫酸化和10 mM硫酸化脱氧胆酸混合物的灌注。与单独使用5 mM非硫酸化脱氧胆酸后相比,这产生了水和钠的净分泌,同时蛋白质和脱氧核糖核酸输出的增加不太明显,微观黏膜损伤也不太显著。最后,5 mM非硫酸化胆酸对水或钠的转运没有影响,但5 mM硫酸化胆酸,其中一个α-羟基被掩盖而两个α-羟基“暴露”,减少了水的转运。这些结果表明硫酸化可防止α-二羟基胆汁酸在结肠中的泻下作用。