Amin D, Gustafson S, Perrone M H
Department of Pharmacology, Rorer Central Research, Horsham, PA 19044.
Biochem Biophys Res Commun. 1988 Dec 15;157(2):530-4. doi: 10.1016/s0006-291x(88)80281-x.
The effects of a potent HMG CoA reductase inhibitor, lovastatin, was studied in male Syrian Golden hamsters. Lovastatin (0.1% in food for 6 days) increased hamster serum triglycerides by 12-fold with 2.4-fold increase in serum cholesterol. On continuous treatment serum triglyceride and cholesterol levels gradually decreased to below control values by 12-18 days. When hamsters were fed a mixture of lovastatin and Na-mevalonate no increase in serum triglyceride was observed. [14C]Cholesterol synthesis was increased by 266-fold in livers of hamsters fed lovastatin for 6 days. The increased synthesis of endogenous mevalonate metabolites may be a reason for the decrease in triglyceride levels after 6 days in our studies. The present study suggests that a mevalonate metabolite(s) is necessary for normal triglyceride metabolism in hamsters.
在雄性叙利亚金仓鼠中研究了一种强效HMG CoA还原酶抑制剂洛伐他汀的作用。洛伐他汀（食物中含0.1%，持续6天）使仓鼠血清甘油三酯增加了12倍，血清胆固醇增加了2.4倍。持续治疗12 - 18天后，血清甘油三酯和胆固醇水平逐渐降至对照值以下。当给仓鼠喂食洛伐他汀和甲羟戊酸钠的混合物时，未观察到血清甘油三酯增加。喂食洛伐他汀6天的仓鼠肝脏中[14C]胆固醇合成增加了266倍。内源性甲羟戊酸代谢产物合成增加可能是我们研究中6天后甘油三酯水平下降的一个原因。本研究表明，甲羟戊酸代谢产物对于仓鼠正常的甘油三酯代谢是必需的。
