Kusama H, Nishiyama M, Matsubara Y, Ikeda S
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan.
Nihon Yakurigaku Zasshi. 1988 Sep;92(3):181-91. doi: 10.1254/fpj.92.181.
The mechanism of the hypolipidemic action of bezafibrate was investigated in rats. Bezafibrate decreased the incorporation of 14C-acetic acid into the liver and serum triglyceride and inhibited liver acetyl CoA carboxylate activity. Bezafibrate increased liver beta-oxidation, but it had no effect on lipolysis and triglyceride secretion from the liver. Bezafibrate accelerated the elimination of serum triglyceride in Intralipid injected rats and increased tissue lipoprotein lipase activity. Bezafibrate decreased the incorporation of 14C-acetic acid into liver cholesterol and inhibited liver HMG-CoA reductase activity. Bezafibrate had no effect on cholesterol absorption and excretion. These results suggest that the hypotriglyceridemic actions of bezafibrate are due to inhibition of triglyceride synthesis and acceleration of triglyceride elimination and that the hypocholesterolemic action of bezafibrate is mainly due to inhibition of liver HMG-CoA reductase activity.
在大鼠中研究了苯扎贝特的降血脂作用机制。苯扎贝特减少了14C-乙酸掺入肝脏和血清甘油三酯中,并抑制了肝脏乙酰辅酶A羧化酶活性。苯扎贝特增加了肝脏的β-氧化,但对脂解和肝脏甘油三酯分泌没有影响。苯扎贝特加速了注射脂肪乳剂的大鼠血清甘油三酯的清除,并增加了组织脂蛋白脂肪酶活性。苯扎贝特减少了14C-乙酸掺入肝脏胆固醇中,并抑制了肝脏HMG-CoA还原酶活性。苯扎贝特对胆固醇的吸收和排泄没有影响。这些结果表明,苯扎贝特的降甘油三酯作用是由于抑制甘油三酯合成和加速甘油三酯清除,而苯扎贝特的降胆固醇作用主要是由于抑制肝脏HMG-CoA还原酶活性。