Kuipers F, Spanjer H H, Havinga R, Scherphof G L, Vonk R J
Biochim Biophys Acta. 1986 May 21;876(3):559-66. doi: 10.1016/0005-2760(86)90044-5.
Hepatic cholesterol metabolism was studied in rats with a permanent biliary drainage. Three cholesterol vehicles were used to discriminate between metabolic pathways of cholesterol in the liver. [3H]Cholesterol was administered intravenously associated with rat serum lipoproteins, multilamellar (MLV) or small unilamellar (SUV) liposomes. The liposomes were made from cholesterol, sphingomyelin and phosphatidylserine in a 5:4:1 molar ratio. Initial blood elimination differed markedly for the three vehicles: 15 min after injection the 3H radioactivity content of blood for MLV, SUV and lipoprotein was 3, 50 and 54% of the injected dose, respectively. After about 30 min, MLV-cholesterol label started to reappear in the blood, probably after processing of the vehicle by the Kupffer cells. For all vehicles about 80% of the cholesterol label had been excreted in bile after 120 h, predominantly as bile acids. Initial biliary excretion was highest for lipoproteins (5.7% at 1 h), followed by MLV and SUV (1.3 and 1.2%, respectively). No differences in the radioactivity of excreted bile acids were detectable between the three vehicles at 12 h after injection. However, at 1 h the radioactivity in the muricholic acid fraction was markedly increased, as compared to the other bile acids after injection of SUV-cholesterol, but not after injection of MLV- or lipoprotein-cholesterol. Also, the glycine/taurine conjugation ratio of bile acids was increased for SUV-cholesterol at 1 h as compared to that for the other two vehicles. Since SUV appear to donate their cholesterol to a pool which preferentially supplies cholesterol for muricholic acid synthesis, we conclude that more than one cholesterol pool exists in the hepatocytes from which cholesterol can be recruited for bile acid synthesis. Zonal heterogeneity might be responsible for the observed differences.
在永久性胆汁引流的大鼠中研究了肝脏胆固醇代谢。使用了三种胆固醇载体来区分肝脏中胆固醇的代谢途径。[3H]胆固醇与大鼠血清脂蛋白、多层（MLV）或小单层（SUV）脂质体静脉注射给药。脂质体由胆固醇、鞘磷脂和磷脂酰丝氨酸按5:4:1的摩尔比制成。三种载体的初始血液清除率明显不同：注射后15分钟，MLV、SUV和脂蛋白的血液3H放射性含量分别为注射剂量的3%、50%和54%。大约30分钟后，MLV-胆固醇标记开始重新出现在血液中，可能是在库普弗细胞对载体进行处理之后。对于所有载体，120小时后约80%的胆固醇标记物以胆汁酸的形式排泄到胆汁中。初始胆汁排泄率脂蛋白最高（1小时时为5.7%），其次是MLV和SUV（分别为1.3%和1.2%）。注射后12小时，三种载体之间排泄的胆汁酸放射性没有差异。然而，在1小时时，注射SUV-胆固醇后，与其他胆汁酸相比，鼠胆酸部分的放射性明显增加，但注射MLV-胆固醇或脂蛋白-胆固醇后没有这种情况。此外，与其他两种载体相比，SUV-胆固醇在1小时时胆汁酸的甘氨酸/牛磺酸结合率增加。由于SUV似乎将其胆固醇捐赠给一个优先为鼠胆酸合成提供胆固醇的池，我们得出结论，肝细胞中存在不止一个胆固醇池，从中可以招募胆固醇用于胆汁酸合成。区域异质性可能是观察到的差异的原因。
