Akiyoshi T, Uchida K, Takase H, Nomura Y, Takeuchi N
J Lipid Res. 1986 Sep;27(9):915-24.
Normal and alloxan-diabetic male mice (Crj-ICR) were fed a diet containing 0.5% cholesterol for 5 and 10 weeks, and gallbladder bile was analyzed for cholesterol, phospholipids and bile acids, feces for sterols and bile acids, and plasma and liver for cholesterol, phospholipids, and triglycerides. Normal mice developed no gallstones but the diabetic mice developed cholesterol gallstones with an incidence of 70% by 5 weeks and 80% by 10 weeks after feeding of the cholesterol diet. Diabetic mice fed the ordinary diet also developed stones (23%) by 10 weeks. In the diabetic mice, the gallbladder was enlarged about threefold, and biliary lipid concentration, diet intake, and fecal excretion of sterols and bile acids increased but body weight decreased. Cholic acid and beta-muricholic acid comprised over 40% each of the total biliary bile acids in normal mice, but cholic acid increased to about 80% and beta-muricholic acid decreased to a few percent in the diabetic mice. Fecal excretion of bile acids increased after cholesterol feeding in both normal and diabetic mice, but the increased bile acid in the normal animals was beta-muricholic acid and that in the diabetic mice was deoxycholic acid. The mice that developed gallstones showed a marked increase in biliary cholesterol value and decreases in gallbladder bile and bile acid concentration, but no difference in biliary and fecal bile acid composition, bile acid synthesis, fecal sterols, or plasma and liver lipid levels. Cholesterol absorption was increased in the diabetic mice when examined by plasma 14C/3H ratio and fecal 14C-labeled sterol excretion after a single oral administration of [14C]cholesterol and a simultaneous intravenous injection of [3H]cholesterol. These data led to the conclusion that cholesterol gallstones developed in alloxan-diabetic mice fed excess cholesterol, due to the hyperphagia and the enhancement of cholesterol absorption caused by increases in the synthesis and secretion of cholic acid.
将正常和用四氧嘧啶诱导糖尿病的雄性小鼠（Crj-ICR）喂养含0.5%胆固醇的饮食5周和10周，分析胆囊胆汁中的胆固醇、磷脂和胆汁酸，粪便中的固醇和胆汁酸，以及血浆和肝脏中的胆固醇、磷脂和甘油三酯。正常小鼠未形成胆结石，但糖尿病小鼠在喂食胆固醇饮食后5周胆结石发生率为70%，10周时为80%。喂食普通饮食的糖尿病小鼠在10周时也形成了结石（23%）。在糖尿病小鼠中，胆囊增大约三倍，胆汁脂质浓度、饮食摄入量以及固醇和胆汁酸的粪便排泄增加，但体重下降。正常小鼠中，胆酸和β-鼠胆酸各占总胆汁胆汁酸的40%以上，但在糖尿病小鼠中，胆酸增加到约80%，β-鼠胆酸减少到百分之几。正常和糖尿病小鼠在喂食胆固醇后胆汁酸的粪便排泄均增加，但正常动物中增加的胆汁酸是β-鼠胆酸，而糖尿病小鼠中是脱氧胆酸。形成胆结石的小鼠胆汁胆固醇值显著增加，胆囊胆汁和胆汁酸浓度降低，但胆汁和粪便胆汁酸组成、胆汁酸合成、粪便固醇或血浆和肝脏脂质水平无差异。通过单次口服[14C]胆固醇并同时静脉注射[3H]胆固醇后，检测血浆14C/3H比值和粪便14C标记固醇排泄，发现糖尿病小鼠的胆固醇吸收增加。这些数据得出结论，喂食过量胆固醇的四氧嘧啶诱导糖尿病小鼠形成胆固醇胆结石，是由于食欲亢进以及胆酸合成和分泌增加导致胆固醇吸收增强。
