Ståhlberg D, Reihnér E, Ewerth S, Einarsson K, Angelin B
Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Eur J Clin Pharmacol. 1991;40 Suppl 1:S33-6. doi: 10.1007/BF01409405.
The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment.
在大鼠和人类中研究了苯扎贝特治疗对肝脏胆固醇代谢的影响。在大鼠中，苯扎贝特治疗可抑制胆固醇代谢所涉及的三种关键酶[3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶、胆固醇7α-羟化酶和酰基辅酶A：胆固醇酰基转移酶（ACAT）]的活性，但当活性与肝脏总重量相关时，只有ACAT活性显著降低。在人类中，治疗的血脂正常的胆结石患者的HMG-CoA还原酶活性增加了约两倍。相反，血清中的羊毛甾醇浓度降低，表明胆固醇合成受到抑制。HMG-CoA还原酶活性的增加可能是胆固醇合成中其他一些酶受到抑制的一种代偿作用，因为对肝微粒体的体外研究排除了苯扎贝特对HMG-CoA还原酶的直接抑制作用。ACAT活性没有显著变化，与对照组相比，胆固醇7α-羟化酶活性降低了55%-60%。苯扎贝特治疗对低密度脂蛋白受体结合活性没有影响。
