Palomäki A, Malminiemi K, Solakivi T, Malminiemi O
Department of Internal Medicine, Kanta-Häme Central Hospital, Hämeenlinna, Finland.
J Lipid Res. 1998 Jul;39(7):1430-7.
A randomized, double-masked, placebo-controlled cross-over trial was carried out to evaluate whether ubiquinone supplementation (180 mg daily) corrects impaired defence against initiation of oxidation of low density lipoprotein (LDL) related to effective (60 mg daily) lovastatin treatment. Nineteen men with coronary heart disease and hypercholesterolemia received lovastatin with or without ubiquinone during 6-week periods after wash-out. The depletion times for LDL ubiquinol and reduced alpha-tocopherol were determined during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated diene formation. Compared to mere lovastatin therapy, ubiquinone supplementation lead to a 4.4-fold concentration of LDL ubiquinol (P < 0.0001). In spite of the 49% lengthening in depletion time (P < 0.0001) of LDL ubiquinol, the lag time in copper-mediated oxidation increased only by 5% (P = 0.02). Ubiquinone loading had no statistically significant effect on LDL alpha-tocopherol redox kinetics during high radical flux ex vivo. The faster depletion of LDL ubiquinol and shortened lag time in conjugated diene formation during high-dose lovastatin therapy may, at least partially, be restored with ubiquinone supplementation. However, the observed improvement in LDL antioxidative capacity was scarce, and the clinical relevance of ubiquinone supplementation during statin therapy remains open.
进行了一项随机、双盲、安慰剂对照的交叉试验，以评估补充泛醌（每日180毫克）是否能纠正与有效（每日60毫克）洛伐他汀治疗相关的低密度脂蛋白（LDL）氧化起始防御受损的情况。19名患有冠心病和高胆固醇血症的男性在洗脱期后的6周内接受了洛伐他汀治疗，其中部分患者同时服用或不服用泛醌。在2,2 - 偶氮二（2,4 - 二甲基戊腈）（AMVN）诱导的氧化过程中，测定了LDL泛醇和还原型α - 生育酚的消耗时间。通过快速密度梯度超速离心分离的LDL的铜介导氧化用于测量共轭二烯形成传播阶段的延迟时间。与单纯的洛伐他汀治疗相比，补充泛醌使LDL泛醇浓度提高了4.4倍（P < 0.0001）。尽管LDL泛醇的消耗时间延长了49%（P < 0.0001），但铜介导氧化的延迟时间仅增加了5%（P = 0.02）。在高自由基通量的体外实验中，泛醌负载对LDLα - 生育酚氧化还原动力学没有统计学上的显著影响。高剂量洛伐他汀治疗期间LDL泛醇的更快消耗和共轭二烯形成延迟时间的缩短，至少部分可以通过补充泛醌来恢复。然而，观察到的LDL抗氧化能力的改善并不明显，他汀类药物治疗期间补充泛醌的临床相关性仍不明确。
