McNamara D J, Bloch C A, Botha A, Mendelsohn D
Biochim Biophys Acta. 1985 Mar 6;833(3):412-6. doi: 10.1016/0005-2760(85)90098-0.
Sterol synthesis rates were measured in freshly isolated blood mononuclear leukocytes obtained from familial hypercholesterolemic patients undergoing treatment with either probucol alone or probucol plus cholestyramine. Subjects with heterozygous familial hypercholesterolemia on probucol had a significant 31% reduction in mononuclear cell sterol synthesis rates as compared to control patients; sterol synthesis in cells from homozygous familial hypercholesterolemic patients on probucol did not differ from that in control subjects. Addition of cholestyramine to probucol therapy in heterozygous familial hypercholesterolemic patients caused an increase in sterol synthesis rates equal to but not greater than control values, thus negating the decreased mononuclear leukocyte sterol synthesis associated with probucol administration alone. Probucol treatment effectively decreased plasma cholesterol levels in both homozygous and heterozygous familial hypercholesterolemic subjects; however, the data suggest that the drug may exert different effects on sterol synthesis in peripheral tissues depending upon the presence or absence of cellular receptors for low-density lipoproteins.
在刚分离出的血液单核白细胞中测量了甾醇合成速率，这些细胞取自接受单独普罗布考或普罗布考加考来烯胺治疗的家族性高胆固醇血症患者。接受普罗布考治疗的杂合子家族性高胆固醇血症患者，其单核细胞甾醇合成速率与对照患者相比显著降低了31%；接受普罗布考治疗的纯合子家族性高胆固醇血症患者细胞中的甾醇合成与对照受试者没有差异。在杂合子家族性高胆固醇血症患者的普罗布考治疗中加入考来烯胺，导致甾醇合成速率增加至与对照值相当但不超过对照值，从而抵消了单独使用普罗布考时单核白细胞甾醇合成的减少。普罗布考治疗有效地降低了纯合子和杂合子家族性高胆固醇血症受试者的血浆胆固醇水平；然而，数据表明该药物可能根据低密度脂蛋白细胞受体的存在与否，对外周组织中的甾醇合成产生不同影响。
