Klinkspoor J H, Kuver R, Savard C E, Oda D, Azzouz H, Tytgat G N, Groen A K, Lee S P
Department of Gastroenterology, University of Amsterdam, Academic Medical Center, The Netherlands.
Gastroenterology. 1995 Jul;109(1):264-74. doi: 10.1016/0016-5085(95)90293-7.
BACKGROUND & AIMS: Hypersecretion of gallbladder mucin has been proposed as a pathogenic factor in gallstone formation. We investigated whether mucin secretion is modulated by biliary constituents using normal, well-differentiated dog gallbladder epithelial cells.
Model biles or bile salts were applied to monolayers of epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labeled glycoproteins.
Model biles with different cholesterol saturation indices increased mucin secretion by the cells to an average 251% after 5 hours of incubation (P < 0.01). Mucin secretion remained elevated during a 24-hour period, suggesting a sustained effect on mucin secretion. There was no relation between the cholesterol or phospholipid concentration and the extent of stimulation of mucin secretion. Taurocholate caused a dose-dependent increase in mucin secretion, suggesting that bile salt was the bile component responsible for the stimulatory effect. At a concentration of 0.5 mmol/L, only the more hydrophobic bile salts taurochenodeoxycholate and taurodeoxycholate, but not the hydrophylic bile salts taurocholate and tauroursodeoxycholate, stimulated mucin secretion (P < 0.01).
Bile salts play an important role in the regulation of mucin secretion. A shift in the bile salt composition of bile towards the more hydrophobic bile salts may cause mucin hypersecretion, thereby initiating cholesterol gallstone formation.
胆囊粘蛋白分泌过多被认为是胆结石形成的一个致病因素。我们使用正常、分化良好的犬胆囊上皮细胞，研究胆汁成分是否调节粘蛋白分泌。
将模拟胆汁或胆盐应用于上皮细胞单层。通过测量[3H]N-乙酰-D-葡萄糖胺标记的糖蛋白分泌来研究粘蛋白分泌。
不同胆固醇饱和指数的模拟胆汁在孵育5小时后使细胞的粘蛋白分泌平均增加251%（P < 0.01）。在24小时期间，粘蛋白分泌持续升高，表明对粘蛋白分泌有持续影响。胆固醇或磷脂浓度与粘蛋白分泌刺激程度之间没有关系。牛磺胆酸盐导致粘蛋白分泌呈剂量依赖性增加，表明胆盐是负责刺激作用的胆汁成分。在浓度为0.5 mmol/L时，只有疏水性更强的胆盐牛磺鹅去氧胆酸盐和牛磺脱氧胆酸盐，而不是亲水性胆盐牛磺胆酸盐和牛磺熊去氧胆酸盐，刺激粘蛋白分泌（P < 0.01）。
胆盐在粘蛋白分泌的调节中起重要作用。胆汁胆盐组成向疏水性更强的胆盐转变可能导致粘蛋白分泌过多，从而引发胆固醇性胆结石的形成。
