Peluffo R O, Nervi A M, Brenner R R
Acta Physiol Lat Am. 1981;31(2):119-28.
The effect of clofibrate and ethanol in the rat was studied on the following aspects of lipid composition and metabolism: liver delta 5, delta 6 and delta 9 fatty acid desaturases, fatty acid synthetase and fatty acid desaturase microsomal electron transport chain activity and serum cholesterol, triacylglycerols and high (HDL), low (LDL) and very low density lipoprotein (VLDL) levels. Clofibrate administered for 9 days (0.3% W/W) did not modify the relative composition of liver phospholipids and cholesterol, but did diminish triacylglycerol levels increased by ethanol. This effect could be explained by the possible beta-adrenergic blocking properties of clofibrate or by an increased activity of peroxisomal beta-oxidation. Clofibrate also promoted a decrease in serum cholesterol and triacylglycerol levels, delta 6 desaturase activity and a suppression of the electron transport chain as measured by NADH cytochrome b5 reductase and NADH cytochrome c reductase. The drug increased delta 9 desaturase activity and fatty acid synthetase, while no effect could be found in delta 5 desaturase activity. The hypocholesterolenic effect of clofibrate can not be explained through the delta 6 desaturase inhibition, or the fatty acid synthetase enhancement. Ethanol increased the HDL and VLDL and lowered LDL serum concentrations, while clofibrate reversed these results. Considering that clofibrate could have antiatherosclerotic effect in the rat, it is difficult to explain it through these changes in lipoprotein levels, since according to Miller and Miller low HDL levels are predictive of coronary heart disease.
肝脏Δ5、Δ6和Δ9脂肪酸去饱和酶、脂肪酸合成酶以及脂肪酸去饱和酶微粒体电子传递链活性,还有血清胆固醇、三酰甘油以及高(HDL)、低(LDL)和极低密度脂蛋白(VLDL)水平。给予大鼠9天氯贝丁酯(0.3% W/W)未改变肝脏磷脂和胆固醇的相对组成,但确实降低了由乙醇升高的三酰甘油水平。这种作用可以通过氯贝丁酯可能的β-肾上腺素能阻断特性或过氧化物酶体β-氧化活性增加来解释。氯贝丁酯还促使血清胆固醇和三酰甘油水平降低、Δ6去饱和酶活性降低以及通过NADH细胞色素b5还原酶和NADH细胞色素c还原酶测定的电子传递链受抑制。该药物增加了Δ9去饱和酶活性和脂肪酸合成酶,而对Δ5去饱和酶活性未发现影响。氯贝丁酯的降胆固醇作用不能通过抑制Δ6去饱和酶或增强脂肪酸合成酶来解释。乙醇增加了HDL和VLDL并降低了LDL血清浓度,而氯贝丁酯则使这些结果逆转。鉴于氯贝丁酯在大鼠中可能具有抗动脉粥样硬化作用,很难通过脂蛋白水平的这些变化来解释,因为根据米勒夫妇的观点,低HDL水平可预测冠心病。