Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits

    本试验研究了普罗布考对WHHL家兔治疗前已形成的大动脉粥样硬化的影响。8月龄WHHL家兔接受普罗布考治疗5个月后，与同龄未治疗家兔相比，其动脉损伤面积明显减小（P < 0.05）。相反，普罗布考治疗组与未治疗组的血浆胆固醇变化无显著差异。接受普罗布考治疗5个月家兔的LDL对Cu²⁺诱导的氧化显示出抵制作用。普罗布考治疗显著增加血浆CETP活性（P < 0.05）。免疫组织化学研究显示，在未治疗家兔的动脉损伤区域有大量巨噬细胞聚集，而在普罗布考治疗家兔中，平滑肌细胞对损伤起支配性作用。结果表明，普罗布考能够逆转WHHL家兔的动脉粥样硬化损伤，而普罗布考减轻动物模型动脉粥样硬化的作用除了与其降低血浆胆固醇有关，还与其抗氧化作用有关。

    We examined the effect of probucol on the aortic atherosclerosis already developed in Watanabe heritable             hyperlipidemic (WHHL) rabbits at the initiation of treatment. In WHHL rabbits treated with probucol for 5 months from 8  months old, the lesion area in the aorta was significantly (P< 0.05) reduced when compared with that in untreated animals as well as animals at age 8 months. In contrast, plasma cholesterol levels in the probucol-treated group and untreated   group during the experiment were not significantly different. LDL prepared from rabbits receiving probucol for 5 months  showed resistance to oxidation by copper ions. Plasma CETP activity was significantly (P < 0.05) increased by probucol   treatment. An immunohistochemical study showed that macrophages were abundant in the atherosclerotic lesions of untreated rabbits whereas smooth muscle cells were predominant in lesions of probucol-treated rabbits.These results suggest that   the atherosclerotic lesion in WHHL rabbits can regress when treated by probucol and that the attenuation of              atherosclerosis in this animal involves effects of probucol other than a decrease in plasma cholesterol,for example anti-oxidant activity.