The oxidation hypothesis of atherosclerosis implies that antioxidants are able to inhibit lipoprotein oxidation in the arterial wall and thereby retard atherogenesis. Since most of the animal studies performed have used very high doses of antioxidants, it is to date unknown whether antioxidants are effective antiatherosclerotic agents when given in pharmacological doses. Here we addressed this question using homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits as an animal model of atherosclerosis. The rabbits were divided into four groups, each consisting of ten animals. They received either a standard diet or a diet containing 4.3 mg ubiquinone-10, or 4.3 mg vitamin E or 15 mg probucol/kg body weight daily. After 12 months, the extent of aortic atherosclerosis was assessed as the intima thickness, media thickness and intima-to-media ratio in 14 cross sections equally distributed over the whole aorta. To evaluate the antioxidant effects of the diet, lipophilic and hydrophilic antioxidants, lipids, fatty acids and plasma oxidizability were measured after 0, 3 and 6 months of feeding. We found that supplementation with probucol significantly decreased aortic intima-to-media ratio compared to controls. The antiatherosclerotic action of probucol was accompanied by its beneficial action on plasma oxidizability and some plasma antioxidants. No decrease in aortic atherosclerosis was measured in ubiquinone-10- and vitamin E-supplemented rabbits, despite the fact that both antioxidants decreased plasma oxidizability and ubiquinone-10 increased the plasma levels of antioxidants. Taken together, these data suggest that pharmacological doses of probucol retard atherogenesis in WHHL rabbits by an antioxidant mechanism, while ubiquinone-10 and vitamin E at these dosages are ineffective in this highly hyperlipidaemic model. The measurement of some oxidation-related parameters in plasma, such as lipophilic antioxidants, polyunsaturated fatty acids and lipoprotein oxidizability, may be useful in assessing the risk of atherogenesis in humans.
研究背景：动脉粥样硬化的氧化假说提示抗氧化剂能够抑制动脉壁内脂蛋白氧化剂进而延缓动脉粥样硬化进程。大多数动物试验中使用高剂量抗氧化剂，而对于药理剂量下抗氧化剂能防有效治疗动脉粥样硬化还未可知。
研究对象：同型WHHL家兔作为动脉粥样硬化模型。
分组与给药：每组十只，共四组。分别为标准饮食组，辅酶Q10组（饮食添加4.3mg/kg体重），维生素E（4.3mg/kg体重）和普罗布考组（15mg/kg体重）给药12个月。
评价指标：14个切面的内膜厚度，中膜厚度，内膜厚度/中膜厚度评价动脉粥样硬化程度，饲养0，3和6个月后测定亲水和亲脂性抗氧化剂，脂质，脂肪酸和血浆氧化性评价饮食的抗氧化作用。
结果：与对照组相比，普罗布考能显著降低内膜厚度/中膜厚度，普罗布考的抗动脉粥样硬化作用伴随其对血浆氧化性和血浆抗氧化剂的积极作用；
辅酶Q10和维生素E能够降低血浆氧化性，辅酶Q10能够增加血浆抗氧化剂含量，但两组均为显示出抗动脉粥样硬化作用。
结论：药理剂量下的普罗布考通过抗氧化机制延缓WHHL家兔动脉粥样硬化的进程，而辅酶Q10和维生素E药理剂量下对高脂血症模型无疗效。测定血浆中的氧化相关参数如：亲脂性抗氧化剂，聚不饱和脂肪酸和脂蛋白氧化性对于评价人动脉粥样硬化发生风险具有重要的意义。
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