Seböková E, Klimes I, Hermann M, Minchenko A, Mitková A, Hromadová M
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava.
Ann N Y Acad Sci. 1993 Jun 14;683:183-91. doi: 10.1111/j.1749-6632.1993.tb35705.x.
To assess the possible benefits of combined hypolipidemic therapy (acipimox+marine fish oil) on lipid and lipoprotein metabolism, male Wistar rats were fed for 14 days a high sucrose diet (70 cal% sucrose) alone or a high sucrose diet supplemented with acipimox (0.2 g/100 g diet) and/or fish oil (1 ml orally daily; 30 wt% of n-3 PUFA). Feeding a high sucrose diet increased (control: 61 +/- 6 vs HS: 110 +/- 8 nmol.min-1.mg-1, p < 0.001) the activity of acetyl CoA carboxylase in the liver, this was normalized by fish oil but not acipimox alone (HS+FO: 68 +/- 4; HS+ACI: 95 +/- 4; HS+ACI+FO: 71 +/- 2 nmol.min-1.mg-1). Increased triglyceride concentration in serum and muscle tissue (m. soleus and heart) of high sucrose-fed animals was suppressed equally by fish oil, acipimox, and/or both. The cholesterol-lowering effect of fish oil was also present in the liver (p < 0.005). The cholesterol-lowering action of acipimox was accompanied by the accumulation of cholesterol in the liver (p < 0.005), whereas the combination of acipimox+fish oil did not change the liver cholesterol content. After fish oil the LDL binding capacity of liver plasma membranes was increased 1.6-fold (p < 0.001). LDL receptor activity was significantly decreased in HS+ACI group (p < 0.05), but remained unchanged in HS+FO+ACI-fed animals. In summary, (a) the hypotriglyceridemic effect of fish oil in high sucrose-induced HTG is due to its inhibitory effects at the level of fatty acid synthesis; (b) decreased triglyceride production and output from the liver prevent triglyceride accumulation in muscle tissue; (c) the cholesterol-lowering action of acipimox but not fish oil was accompanied by an accumulation of cholesterol in the liver; (d) the latter phenomenon may be due to the opposite effects of both drugs on cholesterol catabolism via hepatic LDL receptors.
为评估联合降脂疗法（阿西莫司+鱼油）对脂质和脂蛋白代谢的潜在益处，将雄性Wistar大鼠单独喂食高蔗糖饮食（70%热量来自蔗糖）14天，或喂食添加阿西莫司（0.2 g/100 g饮食）和/或鱼油（每日口服1 ml；n-3多不饱和脂肪酸含量为30 wt%）的高蔗糖饮食。喂食高蔗糖饮食会增加肝脏中乙酰辅酶A羧化酶的活性（对照组：61±6 vs高蔗糖组：110±8 nmol·min⁻¹·mg⁻¹，p<0.001），鱼油可使其恢复正常，但单独使用阿西莫司则不能（高蔗糖+鱼油组：68±4；高蔗糖+阿西莫司组：95±4；高蔗糖+阿西莫司+鱼油组：71±2 nmol·min⁻¹·mg⁻¹）。高蔗糖喂养动物血清和肌肉组织（比目鱼肌和心脏）中甘油三酯浓度的升高，同样受到鱼油、阿西莫司和/或两者的抑制。鱼油的降胆固醇作用在肝脏中也存在（p<0.005）。阿西莫司的降胆固醇作用伴随着肝脏中胆固醇的积累（p<0.005），而阿西莫司+鱼油的组合并未改变肝脏胆固醇含量。给予鱼油后，肝细胞膜的低密度脂蛋白结合能力增加了1.6倍（p<0.001）。在高蔗糖+阿西莫司组中，低密度脂蛋白受体活性显著降低（p<0.05），但在高蔗糖+鱼油+阿西莫司喂养的动物中保持不变。总之，（a）鱼油在高蔗糖诱导的高甘油三酯血症中的降甘油三酯作用，是由于其在脂肪酸合成水平的抑制作用；（b）肝脏中甘油三酯生成和输出的减少，可防止甘油三酯在肌肉组织中积累；（c）阿西莫司而非鱼油的降胆固醇作用，伴随着肝脏中胆固醇的积累；（d）后一种现象可能是由于两种药物通过肝脏低密度脂蛋白受体对胆固醇分解代谢的相反作用。
