Bravo E, Ortu G, Rivabene R, Santini M T, Cantafora A
Laboratory of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanitá, Roma, Italy.
Atherosclerosis. 1996 Jan 26;119(2):223-33. doi: 10.1016/0021-9150(95)05651-3.
In this study, perfused livers from Yoshida rats, either on a normal diet or on a diet with 0.3% probucol, were examined. The analysis of liver lipid content and of bile and lipoprotein secretion changes showed that probucol had a relevant effect on liver lipid biosynthesis. In particular, it reduced the production of triacylglycerols and, to a much greater extent that of cholesterol. In addition, probucol reduced plasma cholesterol concentration by decreasing esterified cholesterol in HDL1 and HDL2 fractions. Furthermore, HDL1 composition of both hepatic neosynthetized and circulating particles was strongly modified by probucol. Finally, probucol did not appear to induce significant differences in lipid bile secretion while phospholipid secretion from perfused livers was increased. These facts suggest that the hypolipidemic action of probucol is not mediated by an increase in bile steroid secretion, but rather by a direct reduction in hepatic lipoprotein cholesterol secretion. This secretion induces a modified plasma profile of HDL particles such that these variations are advantageous in terms of reverse cholesterol transport.
在本研究中,对正常饮食或食用含0.3%普罗布考饮食的吉田大鼠的灌注肝脏进行了检查。对肝脏脂质含量以及胆汁和脂蛋白分泌变化的分析表明,普罗布考对肝脏脂质生物合成有显著影响。特别是,它降低了三酰甘油的产生,并且在更大程度上降低了胆固醇的产生。此外,普罗布考通过降低HDL1和HDL2组分中的酯化胆固醇来降低血浆胆固醇浓度。此外,普罗布考强烈改变了肝脏新合成的和循环颗粒的HDL1组成。最后,普罗布考似乎并未引起脂质胆汁分泌的显著差异,而灌注肝脏的磷脂分泌增加。这些事实表明,普罗布考的降血脂作用不是通过胆汁类固醇分泌增加来介导的,而是通过直接减少肝脏脂蛋白胆固醇分泌来介导的。这种分泌诱导了HDL颗粒的血浆谱改变,使得这些变化在逆向胆固醇转运方面是有利的。