Fincham J E, Quack G, Wülfroth P, Benadé A J
National Research Programme for Nutritional Intervention, Medical Research Council, Tygerberg, South Africa.
Arzneimittelforschung. 1996 May;46(5):519-25.
In dyslipidemic or hyperlipidemic patients etofibrate (CAS 31637-97-5, active principle of Lipo-Merz-retard) improves plasma lipoprotein profiles by reducing low density lipoprotein cholesterol and triglycerides. Experimentally, it also promotes fibrinolysis and thrombolysis and reduces the susceptibility of lipoproteins to oxidative stress. In order to investigate the possible efficacy of etofibrate on atherosclerosis, a study in African Green Monkeys was performed. To accelerate atherogenesis, balanced groups of adult male Vervetes (Cercopithecus aethiops) were fed an atherogenic diet, with and without etofibrate, while negative controls received a prudent diet. Total dietary risk exposure was 38 months, with etofibrate treatment during the final 27 months. The etofibrate dose achieved plasma concentrations of clofibric acid comparable to the one achieved clinically. Necropsy demonstrated lesions equivalent to human atherosclerosis types I-VII, which were compared between treatments both macroscopically and microscopically. Peripheral atherosclerosis was significantly less frequent after etofibrate treatment than in positive controls. In aortas, etofibrate probably ameliorated atherogenesis, as defined by proliferation of smooth muscle and foam cells, and accumulation of cholesterol crystals. Effective reduction of plasma cholesterol by etofibrate was confirmed. In conclusion, anti-atherogenic efficacy of etofibrate was demonstrated in a non-human primate model of accelerated atherogenesis. The results on peripheral atherosclerosis confirm the preliminary clinical data in patients suffering from peripheral vascular occlusion.
在血脂异常或高脂血症患者中，益多脂（化学物质登录号：31637-97-5，利宝美降脂长效片的活性成分）可通过降低低密度脂蛋白胆固醇和甘油三酯来改善血浆脂蛋白谱。在实验中，它还能促进纤维蛋白溶解和血栓溶解，并降低脂蛋白对氧化应激的易感性。为了研究益多脂对动脉粥样硬化的潜在疗效，我们在非洲绿猴身上进行了一项研究。为了加速动脉粥样硬化的形成，将成年雄性绿猴（非洲长尾猴）分为均衡的几组，分别给予致动脉粥样硬化饮食，其中一组添加益多脂，另一组不添加，而阴性对照组则给予合理饮食。总的饮食风险暴露期为38个月，益多脂治疗在最后27个月进行。益多脂的剂量所达到的氯贝酸血浆浓度与临床上所达到的浓度相当。尸检显示有相当于人类动脉粥样硬化I-VII型的病变，对不同治疗组的病变进行了宏观和微观比较。益多脂治疗后外周动脉粥样硬化的发生率明显低于阳性对照组。在主动脉中，益多脂可能改善了动脉粥样硬化的形成，其表现为平滑肌和泡沫细胞的增殖以及胆固醇晶体的积聚。益多脂有效降低血浆胆固醇得到了证实。总之，在加速动脉粥样硬化的非人灵长类动物模型中证实了益多脂的抗动脉粥样硬化疗效。关于外周动脉粥样硬化的结果证实了外周血管闭塞患者的初步临床数据。
