Fromm H
Department of Medicine, George Washington University, Washington, D.C. 20037.
Dig Dis Sci. 1989 Dec;34(12 Suppl):21S-23S. doi: 10.1007/BF01536658.
Several studies in the hamster model were undertaken to investigate known and recently disclosed metabolic interactions between bile acids and lipoproteins, particularly between ursodiol and low-density-lipoprotein (LDL) receptors. Three groups of animals, receiving a control 0.027% cholesterol diet, supplementation with 0.1% ursodiol, or supplementation with 0.1% chenodeoxycholic acid, were treated for four weeks. Both bile acids suppressed bile acid synthesis. Chenodeoxycholic acid significantly increased serum total cholesterol compared to ursodiol, and high-density-lipoprotein (HDL) cholesterol decreased significantly with chenodeoxycholic acid compared to ursodiol and control. Since the rate of bile acid synthesis is known to influence LDL receptor activity, LDL uptake under these conditions of synthesis suppression was measured. The animals received infusions of hamster LDL and methylated human LDL. Uptake of hamster LDL (occurring by both receptor-dependent and receptor-independent mechanisms) was significantly higher in the ursodiol-treated group than in the others. Human LDL uptake (occurring only by receptor-independent mechanisms) was not significantly affected by either treatment. The mechanisms by which ursodiol apparently directly stimulates the LDL receptor remain speculative but may involve alteration of cell membrane fluidity, change in the rate of LDL receptor cycling, and increase in the number of LDL receptors.
开展了几项仓鼠模型研究，以调查胆汁酸与脂蛋白之间已知的以及最近披露的代谢相互作用，特别是熊去氧胆酸与低密度脂蛋白（LDL）受体之间的相互作用。三组动物分别接受对照0.027%胆固醇饮食、补充0.1%熊去氧胆酸或补充0.1%鹅去氧胆酸，治疗四周。两种胆汁酸均抑制胆汁酸合成。与熊去氧胆酸相比，鹅去氧胆酸显著增加血清总胆固醇，与熊去氧胆酸和对照组相比，鹅去氧胆酸使高密度脂蛋白（HDL）胆固醇显著降低。由于已知胆汁酸合成速率会影响LDL受体活性，因此在这些合成抑制条件下测量了LDL摄取。给动物输注仓鼠LDL和甲基化人LDL。在熊去氧胆酸治疗组中，仓鼠LDL的摄取（通过受体依赖性和受体非依赖性机制发生）显著高于其他组。人LDL摄取（仅通过受体非依赖性机制发生）不受任何一种治疗的显著影响。熊去氧胆酸明显直接刺激LDL受体的机制仍属推测，但可能涉及细胞膜流动性的改变、LDL受体循环速率的变化以及LDL受体数量的增加。
