van Dijk M C, Pieters M, van Berkel T J
Division of Biopharmaceutics, University of Leiden, The Netherlands.
Eur J Biochem. 1993 Feb 1;211(3):781-7. doi: 10.1111/j.1432-1033.1993.tb17609.x.
Chylomicrons labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 25.5: 74.5, were rapidly removed from rat serum in vivo, and taken up predominantly by the parenchymal liver cells (88.2%) of the hepatic uptake at 15 min after injection). Lactoferrin reduced the liver uptake of chylomicron remnants by 72%, at 20 min after injection. It appeared that the free cholesterol which is present in the chylomicrons is not readily exchanged within the used time period with other cholesterol pools in the animal. Between 10-60 min after injection of 3H-labelled chylomicrons, cholesterol esters are hydrolysed in the liver. Appearance of radioactivity in bile was rapid and at 3, 24 and 72 h after injection, 13.4%, 44.0% and 70.0%, respectively, of the injected dose appeared in bile, mainly as bile acids (> 90%). Lactoferrin reduced the biliary secretion of radioactivity, especially during the first hour after injection. The total amount of radioactivity recovered was 58.0% of the injected dose at 72 h after injection. After injection of beta-migrating very low-density lipoprotein labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 23.5:76.5, the maximum amount of radioactivity secreted in bile was much lower than with chylomicrons (2.6% cf. 5.2% at 1 h after injection), although the kinetics of the initial liver association and cholesterol ester hydrolysis were even more rapid. Biliary accumulation of radioactivity was also lower with 50.5% of the injected dose recovered at 72 h after injection. It can be concluded from these studies that the processing of chylomicron remnant cholesterol components in the liver and the subsequent secretion in the bile mainly as bile acids is very efficient. The efficient liver uptake of chylomicron remnants by the liver remnant receptor is thereby essential to achieve this high percentage of removal, thus protecting against extrahepatic cholesterol (ester) deposition.
以25.5:74.5的比例标记有[³H]胆固醇/[³H]胆固醇酯的乳糜微粒在体内能迅速从大鼠血清中清除，并在注射后15分钟主要被肝实质细胞摄取（占肝脏摄取量的88.2%）。乳铁蛋白在注射后20分钟时可使肝脏对乳糜微粒残粒的摄取减少72%。似乎乳糜微粒中存在的游离胆固醇在所用时间段内不易与动物体内的其他胆固醇池进行交换。在注射³H标记的乳糜微粒后10 - 60分钟内，胆固醇酯在肝脏中被水解。胆汁中放射性物质出现迅速，在注射后3小时、24小时和72小时，分别有13.4%、44.0%和70.0%的注射剂量出现在胆汁中，主要以胆汁酸形式存在（>90%）。乳铁蛋白减少了放射性物质的胆汁分泌，尤其是在注射后的第一小时内。注射后72小时回收的放射性物质总量为注射剂量的58.0%。以23.5:76.5的比例标记有[³H]胆固醇/[³H]胆固醇酯的β-迁移极低密度脂蛋白注射后，胆汁中分泌的最大放射性物质含量远低于乳糜微粒（注射后1小时分别为2.6%对比5.2%），尽管最初肝脏结合和胆固醇酯水解的动力学过程甚至更快。注射后72小时回收的注射剂量的50.5%也表明胆汁中放射性物质的积累较低。从这些研究可以得出结论，肝脏中乳糜微粒残粒胆固醇成分的处理以及随后主要以胆汁酸形式分泌到胆汁中是非常有效的。肝脏通过残粒受体对乳糜微粒残粒的有效摄取对于实现如此高比例的清除至关重要，从而防止肝外胆固醇（酯）沉积。
