Scobey M W, Johnson F L, Rudel L L
Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Am J Physiol. 1989 Oct;257(4 Pt 1):G644-52. doi: 10.1152/ajpgi.1989.257.4.G644.
The movement of cholesterol from high-density lipoproteins (HDL) into bile has been studied using perfused livers from cholesterol-fed African Green monkeys. Mass amounts of HDL were isolated from the plasma of African Green monkeys and were doubly labeled with either 125I-apolipoprotein and [3H]cholesteryl ester or with [3H]cholesteryl ester and [14C]cholesterol. For 3 h of perfusion HDL-free cholesterol was cleared from perfusate at a faster rate than HDL ester cholesterol which, in turn, was cleared at a faster rate than HDL protein. [14C]cholesterol from HDL appeared in biliary bile acids and cholesterol at a higher rate than [3H]esterified cholesterol from HDL. The specific activities of biliary [14C]cholesterol and HDL-free [14C]cholesterol had equilibrated by 60 min of perfusion, although the specific activity of whole liver free [14C]cholesterol was still only 46% of that in bile at 180 min of perfusion. In contrast, the specific activity of total liver free [3H]cholesterol was equal to that of biliary [3H]cholesterol by 180 min of perfusion. We conclude that, in this primate model, HDL-free cholesterol enters into a hepatic compartment that communicates with biliary cholesterol and bile acid precursor pools more efficiently than with other liver pools of cholesterol, whereas HDL-esterified cholesterol appears to mix with all liver pools with equal efficiency. Overall, these data support the concept of compartmentalization of cholesterol in the liver.
利用胆固醇喂养的非洲绿猴的灌注肝脏,对胆固醇从高密度脂蛋白(HDL)进入胆汁的过程进行了研究。从非洲绿猴的血浆中分离出大量HDL,并用125I-载脂蛋白和[3H]胆固醇酯或[3H]胆固醇酯和[14C]胆固醇进行双重标记。在3小时的灌注过程中,灌注液中HDL游离胆固醇的清除速度比HDL酯胆固醇快,而HDL酯胆固醇的清除速度又比HDL蛋白快。HDL中的[14C]胆固醇以比HDL中的[3H]酯化胆固醇更高的速率出现在胆汁酸和胆汁胆固醇中。灌注60分钟时,胆汁中[14C]胆固醇和HDL游离[14C]胆固醇的比活性达到平衡,尽管在灌注180分钟时,全肝游离[14C]胆固醇的比活性仍仅为胆汁中的46%。相比之下,灌注180分钟时,全肝游离[3H]胆固醇的比活性与胆汁中[3H]胆固醇的比活性相等。我们得出结论,在这个灵长类动物模型中,HDL游离胆固醇进入一个肝区室,该肝区室与胆汁胆固醇和胆汁酸前体池的沟通比与肝脏其他胆固醇池更有效,而HDL酯化胆固醇似乎以相同效率与所有肝脏池混合。总体而言,这些数据支持肝脏中胆固醇分隔化的概念。