Smit M J, Kuipers F, Vonk R J, Temmerman A M, Jäckle S, Windler E E
Department of Pediatrics, University of Groningen, The Netherlands.
Hepatology. 1993 Mar;17(3):445-54.
We have studied the coupling between hepatic uptake of chylomicron remnant cholesteryl ester and biliary excretion of cholesterol and bile acids in rats, after feeding them a cholesterol-free (control) or a high-cholesterol diet (1% wt/wt) for 2 wk. We equipped rats with permanent catheters in the bile duct, duodenum and heart to allow experiments in unanesthetized, unrestrained animals. Cholesterol feeding induced a 20% increase in plasma cholesterol concentration, a threefold increase in hepatic bile acid synthesis and a 27% increase in bile acid pool size, whereas biliary excretion of cholesterol was decreased by 50%. The enlarged bile acid pool contained relatively less cholic acid and more chenodeoxycholic acid and muricholic acids. [3H]cholesteryl ester-labeled chylomicron remnants (150 micrograms protein per rat) were injected intracardially, and blood and bile were collected for a period of 22 hr. Plasma disappearance of remnants was significantly delayed by cholesterol feeding, probably caused by competition with diet-induced beta-very low density lipoproteins for hepatic uptake. In control rats biliary excretion of chylomicron remnant-derived radioactivity (50% in free cholesterol and 50% in bile acids) showed an initial peak 1 hr after injection (2.4% dose per hour). A second peak (90% in bile acids), amounting to 1.5% of the dose per hour, appeared 11 hr after injection. Total 22-hr excretion of 3H was 22% of the dose. In cholesterol-fed rats chylomicron remnant-derived radioactivity appeared more rapidly in bile, with a peak 1 hr after injection, amounting to 3.5% of the dose per hour. In this case radioactivity was mainly present as bile acid. Total excretion in 22 hr was 27% of the dose. We conclude that chylomicron remnant uptake by the liver is efficiently coupled to bile acid synthesis and biliary excretion, thus providing an efficient pathway for removal of intestine-derived cholesterol. After cholesterol feeding, chylomicron remnant cholesteryl ester is more efficiently converted to bile acids, a mechanism which may contribute to the resistance of rats to diet-induced elevation of plasma cholesterol. In contrast, biliary excretion in the form of free cholesterol, the second main excretory pathway, is significantly decreased by a high-cholesterol diet.
我们研究了给大鼠喂食无胆固醇（对照）或高胆固醇饮食（1%重量/重量）2周后，乳糜微粒残粒胆固醇酯的肝脏摄取与胆固醇及胆汁酸的胆汁排泄之间的耦合关系。我们给大鼠的胆管、十二指肠和心脏植入永久性导管，以便在未麻醉、不受约束的动物身上进行实验。喂食胆固醇导致血浆胆固醇浓度升高20%，肝脏胆汁酸合成增加三倍，胆汁酸池大小增加27%，而胆固醇的胆汁排泄减少了50%。扩大的胆汁酸池中胆酸相对较少，鹅脱氧胆酸和鼠胆酸较多。给大鼠心内注射[3H]胆固醇酯标记的乳糜微粒残粒（每只大鼠150微克蛋白质），并在22小时内收集血液和胆汁。喂食胆固醇显著延迟了残粒在血浆中的消失，这可能是由于与饮食诱导的β-极低密度脂蛋白竞争肝脏摄取所致。在对照大鼠中，乳糜微粒残粒衍生放射性物质的胆汁排泄（游离胆固醇中占50%，胆汁酸中占50%）在注射后1小时出现初始峰值（每小时2.4%剂量）。第二个峰值（胆汁酸中占90%）在注射后11小时出现，每小时占剂量的1.5%。3H的22小时总排泄量为剂量的22%。在喂食胆固醇的大鼠中，乳糜微粒残粒衍生的放射性物质在胆汁中出现得更快，在注射后1小时出现峰值，每小时占剂量的3.5%。在这种情况下，放射性物质主要以胆汁酸的形式存在。22小时的总排泄量为剂量的27%。我们得出结论，肝脏对乳糜微粒残粒的摄取与胆汁酸合成及胆汁排泄有效耦合，从而为清除肠道来源的胆固醇提供了一条有效途径。喂食胆固醇后，乳糜微粒残粒胆固醇酯能更有效地转化为胆汁酸，这一机制可能有助于大鼠抵抗饮食诱导的血浆胆固醇升高。相比之下,作为第二条主要排泄途径的游离胆固醇形式的胆汁排泄，会因高胆固醇饮食而显著减少。
