Cohen B I, Matoba N, Mosbach E H, Ayyad N, Hakam K, Suh S O, McSherry C K
Department of Surgery, Beth Israel Medical Center, New York, New York.
Gastroenterology. 1990 Feb;98(2):397-405. doi: 10.1016/0016-5085(90)90831-k.
The aim of the present study is to examine the efficacy of 6-hydroxy substituted bile acids on the prevention of cholesterol gallstones in a new hamster model of cholesterol cholelithiasis. Male golden Syrian hamsters were fed a nutritionally adequate semipurified lithogenic diet consisting of casein, cornstarch, soluble starch, butterfat, corn oil, and cellulose plus 0.3% cholesterol. Six different bile acids were added to this diet at the 0.05% level: chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid, murideoxycholic acid, 6 beta-methyl-hyodeoxycholic acid, and 6 alpha-methyl-murideoxycholic acid. At the end of the 6-wk feeding period, the control group receiving the lithogenic diet had a 55% incidence of gallstones. It was found that all bile acids had inhibited the formation of cholesterol gallstones; complete prevention of gallstones was observed with all 4 3,6-dihydroxy bile acids, whereas chenodeoxycholic acid and ursodeoxycholic acid were somewhat less effective (80% and 75% prevention, respectively). The accumulation of cholesterol in serum and liver induced by the lithogenic diet was inhibited to some extent by all of the bile acids; hyodeoxycholic acid, murideoxycholic acid, and 6 beta-methyl hyodeoxycholic acid were most effective in this respect. The administered bile acids tended to predominate in bile in the case of chenodeoxycholic acid, hyodeoxycholic acid, and 6 beta-methyl-hyodeoxycholic acid. In contrast, ursodeoxycholic acid seemed to be converted to chenodeoxycholic acid and murideoxycholic acid to hyodeoxycholic acid. Only 4% of the 6-methyl analogue of murideoxycholic acid, 6 alpha-methyl-murideoxycholic acid, was recovered in gallbladder bile. These experiments show that the new hamster model of cholesterol cholelithiasis is suitable for gallstone-prevention studies. It was not possible to draw definite conclusions concerning the mechanism of action of the administered bile acids on the basis of cholesterol saturation or the presence of liquid crystals. The detailed mechanism of gallstone prevention by hydrophilic bile acids in this model remains to be elucidated.
本研究的目的是在一种新的胆固醇结石病仓鼠模型中，检验6-羟基取代胆汁酸对预防胆固醇胆结石的功效。给雄性金黄叙利亚仓鼠喂食一种营养充足的半纯化致石性饮食，该饮食由酪蛋白、玉米淀粉、可溶性淀粉、乳脂肪、玉米油、纤维素以及0.3%胆固醇组成。在该饮食中添加0.05%水平的六种不同胆汁酸：鹅去氧胆酸、熊去氧胆酸、猪去氧胆酸、鼠去氧胆酸、6β-甲基猪去氧胆酸和6α-甲基鼠去氧胆酸。在6周喂养期结束时，接受致石性饮食的对照组胆结石发病率为55%。发现所有胆汁酸均抑制了胆固醇胆结石的形成；所有4种3,6-二羟基胆汁酸均观察到完全预防胆结石的效果，而鹅去氧胆酸和熊去氧胆酸的效果稍差（分别为80%和75%的预防率）。所有胆汁酸均在一定程度上抑制了致石性饮食诱导的血清和肝脏中胆固醇的蓄积；猪去氧胆酸、鼠去氧胆酸和6β-甲基猪去氧胆酸在这方面最为有效。在鹅去氧胆酸、猪去氧胆酸和6β-甲基猪去氧胆酸的情况下，所给予的胆汁酸往往在胆汁中占主导。相比之下，熊去氧胆酸似乎转化为鹅去氧胆酸，鼠去氧胆酸转化为猪去氧胆酸。在胆囊胆汁中仅回收了4%的鼠去氧胆酸6-甲基类似物6α-甲基鼠去氧胆酸。这些实验表明，新的胆固醇结石病仓鼠模型适用于胆结石预防研究。基于胆固醇饱和度或液晶的存在，无法就所给予胆汁酸的作用机制得出明确结论。亲水性胆汁酸在该模型中预防胆结石的详细机制仍有待阐明。
