Uchida K, Satoh T, Takase H, Nomura Y, Takasu N, Kurihara H, Takeuchi N
Strategic Information Unit, Shionogi & Co., Ltd., Tokyo, Japan.
J Atheroscler Thromb. 1996;3(1):52-8. doi: 10.5551/jat1994.3.52.
Normal and alloxan diabetic rats were kept on a 0.25% cholesterol diet for 12 months and the changes in serum cholesterol levels, and fecal excretion of sterols and bile acids were examined to elucidate the influence of changes in bile acid metabolism on manifestations of hypercholesterolemia and development of atheromatous lesions. Diabetic rats fed the cholesterol diet showed increases in bile acid synthesis and in the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio, and developed significant hypercholesterolemia and atheromatous lesions. In contrast, normal rats showed increased bile acids synthesis but a decreased CA/CDCA ratio after feeding with the cholesterol diet, and developed neither hypercholesterolemia nor atheromatous lesions. Fecal sterol excretion and the cholesterol/sitosterol ratio decreased in diabetic rats. Positive correlations were found between the cumulative serum cholesterol level and the atheromatous lesion area, and between the fecal CA/CDCA ratio and the serum cholesterol level, in the latter of which the correlation was higher in rats on the cholesterol diet than in those on the standard diet. These findings suggest that alteration of bile acid metabolism with increases in cholic acid synthesis and CA/CDCA ratio in diabetic rats enhances cholesterol absorption to produce significant hypercholesterolemia, which in turn leads to development of atheromatous lesions.
将正常大鼠和四氧嘧啶糖尿病大鼠置于含0.25%胆固醇的饮食环境中饲养12个月，检测血清胆固醇水平变化以及粪便中固醇和胆汁酸的排泄情况，以阐明胆汁酸代谢变化对高胆固醇血症表现和动脉粥样硬化病变发展的影响。喂食胆固醇饮食的糖尿病大鼠胆汁酸合成增加，胆酸组/鹅去氧胆酸组（CA/CDCA）比值升高，并出现显著的高胆固醇血症和动脉粥样硬化病变。相比之下，正常大鼠喂食胆固醇饮食后胆汁酸合成增加，但CA/CDCA比值降低，既未出现高胆固醇血症也未出现动脉粥样硬化病变。糖尿病大鼠粪便中固醇排泄量以及胆固醇/谷甾醇比值降低。血清胆固醇累积水平与动脉粥样硬化病变面积之间，以及粪便CA/CDCA比值与血清胆固醇水平之间均呈正相关，其中喂食胆固醇饮食的大鼠相关性高于喂食标准饮食的大鼠。这些研究结果表明，糖尿病大鼠胆汁酸代谢改变，胆酸合成和CA/CDCA比值增加，增强了胆固醇吸收，从而产生显著的高胆固醇血症，进而导致动脉粥样硬化病变的发展。
