Quarfordt S H, Oswald B S, Farouk M O, Wehrenberg D C, Morton E B, Landis B A
Department of Medicine, Durham Veterans Affairs, Medical Center, North Carolina 27705.
J Clin Invest. 1993 Jun;91(6):2532-8. doi: 10.1172/JCI116489.
The clearance of particulate triglyceride from the plasma of cholesterol-fed rats with appreciable stores of hepatic cholesterol ester produces a substantial increment in plasma cholesterol. Most of this plasma cholesterol increment arises from existing tissue sources. The increment begins from 4 to 6 h after clearance and is due to the appearance of larger cholesterol-rich, triglyceride-poor, beta migrating lipoproteins, which are isolated in the d < 1.063 fraction with an apoprotein (Apo) content consisting primarily of Apo E and smaller amounts of Apo B. A concurrent decrease in alpha lipoproteins occurs with the beta lipoprotein increment. Within 1 d of clearance the beta lipoproteins fall and alpha lipoproteins increase. The increase in total plasma Apo E and Apo B initially parallels that of the cholesterol, but it persists even when cholesterol falls. A modest decrease in plasma Apo A1 was observed during the time alpha lipoproteins declined. A significant increase in plasma lecithin cholesterol acyl transferase preceded the increase in beta lipoprotein cholesterol. This enzyme increment was absent in rats with little lipoprotein response despite increased hepatic cholesterol. In vivo inhibition of this enzyme with dithionitrobenzoic acid virtually eliminated the postclearance hypercholesterolemia. Plasma particulate triglyceride clearance induces an increase in beta lipoproteins. Coupling of this clearance and hepatic lipoprotein secretion occurs by an unknown mechanism modulated by lecithin cholesterol acyl transferase.
在肝胆固醇酯储存量可观的情况下，清除喂食胆固醇的大鼠血浆中的颗粒状甘油三酯会使血浆胆固醇大幅增加。这种血浆胆固醇的增加大部分源于现有的组织来源。增加始于清除后4至6小时，是由于出现了更大的富含胆固醇、甘油三酯含量低的β迁移脂蛋白，这些脂蛋白在d<1.063的组分中分离出来，其载脂蛋白（Apo）含量主要由Apo E和少量Apo B组成。随着β脂蛋白增加，α脂蛋白同时减少。清除后1天内，β脂蛋白下降，α脂蛋白增加。血浆总Apo E和Apo B的增加最初与胆固醇的增加平行，但即使胆固醇下降，这种增加仍持续存在。在α脂蛋白下降期间，观察到血浆Apo A1有适度下降。β脂蛋白胆固醇增加之前，血浆卵磷脂胆固醇酰基转移酶有显著增加。尽管肝脏胆固醇增加，但脂蛋白反应很少的大鼠中没有这种酶的增加。用二硫代硝基苯甲酸在体内抑制这种酶实际上消除了清除后的高胆固醇血症。血浆颗粒状甘油三酯清除导致β脂蛋白增加。这种清除与肝脏脂蛋白分泌的耦合通过一种未知机制发生，该机制受卵磷脂胆固醇酰基转移酶调节。
