Suckling K E, Benson G M, Bond B, Gee A, Glen A, Haynes C, Jackson B
Smith Kline Beecham Pharmaceuticals, Welwyn, Herts, U.K.
Atherosclerosis. 1991 Aug;89(2-3):183-90. doi: 10.1016/0021-9150(91)90059-c.
Cholestyramine was administered to hamsters at 6 doses in the diet for 1 week. Plasma cholesterol, LDL + VLDL cholesterol and HDL cholesterol were measured after this period. Bile acid excretion was measured in faeces collected over the final 24 h of the experiment. A dose-response curve for each parameter measured was constructed using data from individual hamsters. For the bile acid and the cholesterol measurements a maximum response was observed at the highest doses. A correlation between the bile acids excreted over 24 h and the LDL + VLDL cholesterol showed that the maximum effect of cholestyramine on lowering plasma and lipoprotein cholesterol occurred at a submaximal excretion level of bile acids. Comparison of the efficiency of cholestyramine in reducing plasma cholesterol in the hamster with limited data in the dog and in man suggest that a greater lowering of plasma cholesterol is achieved in the dog and in man for an equivalent increase in bile acid excretion caused by the sequestrant. As is already known, cholestyramine treatment caused an increase in hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity. Interestingly in this study the novel observation was made that the bile acid sequestrant reduced the activity of hepatic acyl-CoA: cholesterol acyltransferase.
将消胆胺以6种剂量添加到仓鼠的饮食中，持续1周。在此期间结束后，测量血浆胆固醇、低密度脂蛋白 + 极低密度脂蛋白胆固醇和高密度脂蛋白胆固醇。在实验的最后24小时收集的粪便中测量胆汁酸排泄量。使用来自各个仓鼠的数据构建每个测量参数的剂量反应曲线。对于胆汁酸和胆固醇测量，在最高剂量下观察到最大反应。24小时内排泄的胆汁酸与低密度脂蛋白 + 极低密度脂蛋白胆固醇之间的相关性表明，消胆胺降低血浆和脂蛋白胆固醇的最大作用发生在胆汁酸排泄的次最大水平。将仓鼠中消胆胺降低血浆胆固醇的效率与狗和人类的有限数据进行比较表明，对于螯合剂引起的胆汁酸排泄等量增加，狗和人类中血浆胆固醇的降低幅度更大。如已知的那样，消胆胺治疗导致肝胆固醇7α-羟化酶和HMG-CoA还原酶活性增加。有趣的是，在这项研究中发现了一个新的观察结果，即胆汁酸螯合剂降低了肝酰基辅酶A：胆固醇酰基转移酶的活性。
