Podrez E A, Kosykh V A, Lakeev Y V, Kosenkov E I, Mambetisaeva E T, Repin V S, Smirnov V N, Miettinen T A
Cardiology Research Center, Academy of Medical Sciences, Moscow, Russia.
Lipids. 1993 Aug;28(8):709-13. doi: 10.1007/BF02535991.
Two groups of rabbits, either hyperresponsive or hyporesponsive to dietary cholesterol, were selected after ten weeks of cholesterol feeding (0.2 g cholesterol/kg body weight per day). Bile acids and very low density lipoprotein (VLDL) production were determined in primary hepatocyte cultures from control, hyper- and hyporesponsive rabbits. Free cholesterol and cholesteryl ester contents in hepatocytes of the hyperresponsive rabbits was significantly increased. In contrast, lipid composition in hepatocytes of the hyporesponders was similar to that of control cells. Cholic acid was the predominant bile acid in the culture medium of hepatocytes together with small amounts of chenodeoxycholic and deoxycholic acids. The rate of cholic acid production by hepatocytes in the hyporesponsive group was two times higher than that in the hyperresponsive group. Bile acid production by control hepatocytes was slightly higher than in the hyperresponsive group. In contrast, secretion of VLDL cholesteryl ester was significantly increased by hepatocytes of the hyperresponsive rabbits. Similar differences in bile acid production were found between hypo- and hyperresponsive rabbits selected after five days of cholesterol feeding and subsequent maintenance on a low cholesterol diet for a period of one month. The results suggest that the increased rate of bile acid production could contribute to the apparent resistance of hyporesponders to the atherogenic diet.
在给予胆固醇喂养（每天0.2克胆固醇/千克体重）10周后，挑选出两组对膳食胆固醇反应过度或反应不足的兔子。在来自对照、反应过度和反应不足兔子的原代肝细胞培养物中测定胆汁酸和极低密度脂蛋白（VLDL）的产生。反应过度的兔子肝细胞中的游离胆固醇和胆固醇酯含量显著增加。相比之下，反应不足的兔子肝细胞中的脂质组成与对照细胞相似。胆酸是肝细胞培养基中的主要胆汁酸，并伴有少量鹅去氧胆酸和脱氧胆酸。反应不足组肝细胞产生胆酸的速率比反应过度组高两倍。对照肝细胞产生胆汁酸的量略高于反应过度组。相比之下，反应过度的兔子肝细胞分泌的VLDL胆固醇酯显著增加。在给予胆固醇喂养5天后挑选出的反应不足和反应过度的兔子，并随后在低胆固醇饮食中维持1个月，它们之间在胆汁酸产生方面也发现了类似差异。结果表明，胆汁酸产生速率的增加可能导致反应不足的兔子对致动脉粥样化饮食具有明显抗性。
