Einarsson K, Ericsson S, Ewerth S, Reihnér E, Rudling M, Ståhlberg D, Angelin B
Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
Eur J Clin Pharmacol. 1991;40 Suppl 1:S53-8.
Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7 alpha hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation.
考来烯胺或考来替泊对胆汁酸肝肠循环的阻断在许多方面影响肝脏的胆固醇代谢。胆汁酸的合成增加，这体现在胆汁酸合成的限速酶胆固醇7α羟化酶的活性增加了几倍。胆固醇向胆汁酸的代谢增加导致肝细胞对胆固醇的需求增加，肝细胞对此的反应是胆固醇的新合成增加，这体现在HMG-CoA还原酶活性增加了几倍，以及低密度脂蛋白受体的表达增加。结果，血浆中低密度脂蛋白胆固醇的水平降低。极低密度脂蛋白颗粒的肝脏分泌率增加。考来烯胺治疗不影响胆汁脂质的输出或胆汁的胆固醇饱和度，这表明用胆汁酸螯合剂治疗不应与胆结石形成风险增加相关。
