Sato A, Watanabe K, Fukuzumi H, Hase K, Ishida F, Kamei T
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Biochem Pharmacol. 1991 Apr 15;41(8):1163-72. doi: 10.1016/0006-2952(91)90654-n.
The effect of simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma triacylglycerol (TG) levels was studied in rats. Dietary administration of MK-733 (0.055%, w/w) for 7 days significantly (P less than 0.05) reduced plasma TG levels by 30.6% associated with a 44.3% significant (P less than 0.01) reduction in very low density lipoprotein TG (VLDL-TG) as compared to those in the concurrent control rats. Clofibrate (0.08%, w/w) also significantly (P less than 0.05) decreased plasma TG levels by 26.1%. MK-733 did not affect the triacylglycerol secretion rate (TGSR) during 0-1.5 hr after administration of Triton WR-1339, but reduced it by 33.9% during 1.5-3.0 hr. Clofibrate also decreased TGSR during 1.5-3.0 hr. MK-733 increased lipoprotein lipase (LPL) activity in epididymal adipose tissue and thigh muscle by 36.3 and 55.0% respectively. MK-733 significantly (P less than 0.05) increased LPL activity in the post-heparin plasma by 21.5%, although it did not affect hepatic triacylglycerol lipase (H-TGL) activity. Clofibrate did not affect LPL activity in the tissues or LPL and H-TGL activities in the post-heparin plasma. It is considered that the mechanism of plasma TG-lowering effect of MK-733 is the removal of VLDL-TG by an increase in LPL activity in the tissues as well as a decrease in the TGSR.
在大鼠中研究了3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂辛伐他汀（MK-733）对血浆甘油三酯（TG）水平的影响。给予MK-733（0.055%，w/w）饮食7天，与同期对照大鼠相比，显著（P<0.05）降低血浆TG水平30.6%，同时极低密度脂蛋白TG（VLDL-TG）显著（P<0.01）降低44.3%。氯贝丁酯（0.08%，w/w）也显著（P<0.05）降低血浆TG水平26.1%。在给予Triton WR-1339后0-1.5小时内，MK-733不影响甘油三酯分泌率（TGSR），但在1.5-3.0小时内使其降低33.9%。氯贝丁酯在1.5-3.0小时内也降低TGSR。MK-733使附睾脂肪组织和大腿肌肉中的脂蛋白脂肪酶（LPL）活性分别增加36.3%和55.0%。MK-733使肝素后血浆中的LPL活性显著（P<0.05）增加21.5%，尽管它不影响肝脏甘油三酯脂肪酶（H-TGL）活性。氯贝丁酯不影响组织中的LPL活性或肝素后血浆中的LPL和H-TGL活性。据认为，MK-733降低血浆TG的作用机制是通过增加组织中LPL活性以及降低TGSR来清除VLDL-TG。
