Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals
Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals
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DOI：
10.1007/s002280050338
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发表时间：
1997-09-01
影响因子：
2.9
通讯作者：
Hanefeld, M
中科院分区：
文献类型：
--
作者：
Leonhardt, W;Kurktschiev, T;Hanefeld, M
目的：低密度脂蛋白（LDL）的氧化被认为是动脉粥样硬化发生发展的重要环节。微量金属参与氧化过程。这是感兴趣的，以确定是否与氟伐他汀，一种有效的HMGCoA还原酶抑制剂，降脂治疗，影响LDL氧化和微量金属levels.Methods：20例高胆固醇血症患者进行了治疗与氟伐他汀（40毫克，每天两次）或安慰剂8周的双盲，随机研究。结果：经氟伐他汀治疗后，总胆固醇下降24%，甘油三酯下降26%，血浆锌下降8%。Cu、Se、Mn含量变化不显著。LDL经超离心分离。LDL降低18%，LDL-C降低29%，LDL-TG降低19%。LDL中α-生育酚和视黄醇的浓度变化不显著。将LDL制备物与铜离子（204 μ mol . l（-1）LDL-C/3.2 μ mol . 1（-1）Cu），并在234 nm下监测共轭二烯的形成5小时。用氟伐他汀治疗导致二烯产生减少16%，二烯产生率减少14%，效果与安慰剂显著不同（P=0.02）。滞后时间的变化没有达到显著性;但是，它与LDL α-生育酚的变化呈正相关。结论：氟伐他汀具有降脂和抗氧化作用。
Objective: Oxidation of low density lipoproteins (LDL) is thought to be an important step in the development of atherosclerosis. Trace metals are involved in oxidative processes. It was of interest to determine whether lipid-lowering therapy with fluvastatin, a potent HMGCoA reductase inhibitor, affected LDL oxidation and trace metal levels.Methods: Twenty hypercholesterolemic patients were treated with fluvastatin (40 mg twice daily) or placebo for 8 weeks in a double-blind, randomized study. LDL composition, antioxidants and oxidizability as well as plasma zinc, copper, selenium and manganese concentrations were investigated.Results: After fluvastatin treatment, total cholesterol was reduced by 24%, triglycerides fell by 26% and plasma Zn fell by 8%. Cu, Se and Mn changed insignificantly. LDL were separated by ultracentrifugation. LDL were reduced by 18%, LDL-C by 29% and LDL-TG by 19%. The concentrations of alpha-tocopherol and retinol in LDL changed insignificantly. LDL preparations were incubated with copper ions (204 mu mol . l(-1) LDL-C/3.2 mu mol . l(-1) Cu) and formation of conjugated dienes was monitored at 234 nm for 5 h. Treatment with fluvastatin caused a reduction of diene production by 16% and of diene production rate by 14%, effects being significantly different from placebo (P=0.02). The change of the lagtime did not reach significance; however, it was positively correlated with the change in LDL alpha-tocopherol. In the placebo group, no significant effects were observed.Conclusion: Fluvastatin therapy had lipid-lowering and antioxidative effects.