Russell J C, Graham S E, Amy R M, Dolphin P J
Department of Surgery, University of Alberta, Edmonton, Canada.
Eur J Pharmacol. 1998 Jun 5;350(2-3):203-10. doi: 10.1016/s0014-2999(98)00244-1.
Probucol is an antihyperlipidemic agent with antioxidant effects and antiatherosclerotic properties in hypercholesterolemic conditions. The JCR:LA-corpulent strain of rats exhibits all aspects of the human 'metabolic syndrome' characterized by obesity, insulin resistance, hypertriglyceridemia, atherogenesis, and ischemic myocardial damage. Male rats were treated with 100 mg/kg body weight probucol from 6 to 12 weeks or from 6 to 39 weeks of age. Short-term metabolic effects were assessed at 12 weeks and both metabolic and cardiovascular effects at 39 weeks of age. Probucol treatment of corpulent male rats did not reduce plasma lipid concentrations or hyperinsulinemia. The index of severity of intimal lesions of the aortic arch was not different from that of controls, although the lesions appeared to be qualitatively more severe. There were significantly fewer adherent macrophages on the endothelial surface. The endothelial layer was unchanged and smoothly covered the vascular surface, including the intimal lesions. Notwithstanding the extensive atherosclerotic lesions, probucol-treated rats had markedly fewer ischemic myocardial lesions. The cardioprotective effect, possibly due to the antioxidant properties of probucol, appears to occur at the level of the endothelium and occurs in the presence of continuing obesity, hyperinsulinemia, hypertriglyceridemia, and atherosclerosis.
普罗布考是一种抗高脂血症药物，在高胆固醇血症情况下具有抗氧化作用和抗动脉粥样硬化特性。JCR:LA肥胖大鼠品系表现出人类“代谢综合征”的所有特征，包括肥胖、胰岛素抵抗、高甘油三酯血症、动脉粥样硬化形成和缺血性心肌损伤。雄性大鼠在6至12周龄或6至39周龄时接受100mg/kg体重的普罗布考治疗。在12周时评估短期代谢效应，在39周龄时评估代谢和心血管效应。用普罗布考治疗肥胖雄性大鼠并未降低血脂浓度或高胰岛素血症。主动脉弓内膜病变的严重程度指数与对照组无差异，尽管病变在性质上似乎更严重。内皮表面附着的巨噬细胞明显减少。内皮层未改变，平滑地覆盖血管表面，包括内膜病变。尽管存在广泛的动脉粥样硬化病变，但用普罗布考治疗的大鼠缺血性心肌病变明显较少。这种心脏保护作用可能归因于普罗布考的抗氧化特性，似乎发生在内皮水平，并且在持续存在肥胖、高胰岛素血症、高甘油三酯血症和动脉粥样硬化的情况下出现。
