Yamahara J, Chisaka T, Sawada T, Fujimura H
Nihon Yakurigaku Zasshi. 1983 Sep;82(3):171-80.
A study was attempted to establish a screening method for detecting cholelitholytic ingredients from a wide variety of natural substances. Although mice were selected as a suitable pathological model of cholelithiasis to detect a small amount of the ingredients, all the conventional lithogenic diets caused unfavorable influence on the animals. Therefore, as the first step we formulated a new lithogenic diet consisting of butter, cholesterol, cholic acid, etc, which was adequate for mice. Subsequently, the pathological characteristics and persistence of cholelithiasis were examined in the animals; the changes in bile compositions including free and conjugated bile acids, cholesterol and phospholipids were observed before and at the onset of cholelithiasis. Following confirmation of the stone formation, a normal diet was substituted for the lithogenic diet to likewise assess the bile compositions 4 and 6 weeks later. An increasing tendency for deoxycholic acid, disappearance of chenodeoxycholic acid and decrease in ursodeoxycholic acid were seen under the condition of cholelithiasis. In addition, the cholic acid-glycine conjugate which should not exist in the normal state and the increase in free and tauring-conjugated cholic acid were noticed. The biliary cholesterol level in treated mice increased to about 4 times higher than that in untreated mice, while the biliary phospholipids and total bile acids levels increased to only about 1.5 and about 2 times the control levels, respectively. The incidence of stone formation rose sharply at an experimental period between 2 and 3 weeks after starting the lithogenic diet. Gallstones die not disappear even at the 6th week after substituting a normal diet for the lithogenic one. However, the cholic acid-glycine conjugate disappeared, and deoxycholic acid as well as chenodeoxycholic acid and ursodeoxycholic acid tended to recover to the normal levels in the bile.
本研究旨在建立一种从多种天然物质中筛选溶石成分的方法。尽管选择小鼠作为胆结石的合适病理模型以检测少量成分，但所有传统的致石饮食均对动物产生不利影响。因此，作为第一步，我们配制了一种由黄油、胆固醇、胆酸等组成的新型致石饮食，该饮食适合小鼠。随后，检查了动物胆结石的病理特征和持续性；观察了胆结石形成前和形成时胆汁成分的变化，包括游离和结合胆汁酸、胆固醇和磷脂。在确认结石形成后，用正常饮食替代致石饮食，同样在4周和6周后评估胆汁成分。在胆结石形成的情况下，脱氧胆酸呈上升趋势，鹅去氧胆酸消失，熊去氧胆酸减少。此外，还注意到正常状态下不应存在的胆酸 - 甘氨酸共轭物以及游离和牛磺酸共轭胆酸的增加。治疗组小鼠的胆汁胆固醇水平比未治疗组小鼠高出约4倍，而胆汁磷脂和总胆汁酸水平分别仅增加到对照水平的约1.5倍和约2倍。致石饮食开始后2至3周的实验期内，结石形成的发生率急剧上升。即使在将致石饮食替换为正常饮食后的第6周，胆结石也没有消失。然而，胆酸 - 甘氨酸共轭物消失了，脱氧胆酸以及鹅去氧胆酸和熊去氧胆酸的水平在胆汁中趋于恢复到正常水平。
