研究背景：低密度脂蛋白LDL的氧化修饰在动脉粥样硬化形成中起重要作用。HMG-CoA还原酶抑制剂（他汀类）是非常有效的降脂药物，但它同时抑制胆固醇和辅酶Q的生物合成，而其中辅酶Q是线粒体呼吸链中的中间电子载体，其还原形式在人LDL中是有效的天然抗氧化剂。HMG-CoA还原酶抑制剂（他汀类）辛伐他汀治疗小鼠，口服给药30天对肝脏中的高能磷酸盐含量无影响，而对其在心肌中的含量有所降低。

研究目的：研究动脉粥样硬化患者经各种方式治疗后体内LDL对Cu2+诱导氧化的易感性和LDL过氧化自由基产物水平的变化。

方法与结果：维生素400mg/d治疗三个月未降低LDL氧化易感性；普罗布考250mg/d（低剂量）3-6个月治疗未改变血液脂质代谢参数，但显示了强抗氧化性；普伐他汀40mg/d或西立伐他汀0.4mg/d治疗6个月，体内脂质过氧化物大量聚集；普伐他汀和辅酶Q（60mg/d）联合用药能够大大降低LDL脂质过氧化水平；西立伐他汀与普罗布考（250mg/d）联用对LDL脂质过氧化水平无明显影响。

结论：HMG-CoA还原酶抑制剂治疗动脉粥样硬化，联合抗氧化剂治疗能有效抑制动脉粥样硬化中的LDL过氧化。

    The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis.   Drugs of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and          ubiquinone Q10 (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain.It is known that reduced form of ubiquinone Q10 acts in the human LDL as very effective natural antioxidant. Daily per os            administration of HMG-CoA reductase inhibitor simvastatin to rats for 30 day had no effect on high-energy phosphates      (adenosin triphosphate, creatine phosphate) content in liver but decreased a level of these substances in myocardium. We study the Cu2+-mediated susceptibility of human LDL to oxidation and the levels of free radical products of  LDL         lipoperoxidation in LDL particles from patients with atherosclerosis after 3 months treatment with natural antioxidants   vitamin E as well as during 6 months administration of HMG-CoA reductase inhibitors such as pravastatin and cerivastatin in monotherapy and in combination with natural antioxidant ubiquinone Q10 or synthetic antioxidant probucol in a  double-blind placebo-controlled trials. The 3 months of natural antioxidant vitamin E administration (400 mg daily) to patients did not increase the susceptibility of LDL to oxidation. On the other hand, synthetic antioxidant probucol during        long-time period of treatment (3-6 months) in low-dose (250 mg daily) doesn't change the lipid metabolism parameters  in the blood of patients but their high antioxidant activity was observed. Really, after oxidation of probucol-contained    LDL by C-15 animal lipoxygenase in these particles we identified the electron spin resonance signal of probucol phenoxyl radical that suggests the interaction of LDL-associated probucol with lipid radicals in vivo. We observed that 6 months  treatment of patients with pravastatine (40 mg daily) or cerivastatin (0.4 mg daily) was followed by sufficiently        accumulation of LDL lipoperoxides in vivo. In contrast, the 6 months therapy with pravastatin in combination with        ubiquinone Q10 (60 mg daily) sharply decreased the LDL initial lipoperoxides level whereas during treatment with         cerivastatin in combination with probucol (250 mg daily) the LDL lipoperoxides concentration was maintained on an        invariable level. Therefore, antioxidants may be very effective in the prevention of atherogenic oxidative modification  of LDL during HMG-CoA reductase inhibitors therapy.