渡边可遗传高脂血症（WHHL）家兔由于先天低密度脂蛋白受体缺失造成高胆固醇血症并进而发展为早期动脉粥样硬化。普罗布考，具有降脂和抗氧化的双重效应，已经被证实能够降低WHHL家兔动脉粥样硬化的程度。本试验的目的是对普罗布考治疗WHHL家兔引起的动脉粥样硬化病变的细胞和非细胞变化与未治疗组进行对照，并进行详细分析。在两组独立试验中，5只家兔接受添加1%(w/w)普罗布考的饮食饲养，4只作为空白对照， 2只家兔（分别为2和4个月龄）在治疗前被处死界定动脉粥样硬化的基线水平。对每只动物主动脉的30个横切面通过形态测定分析肉眼可见斑块区域的斑块面积，厚度以及组织结构。
普罗布考治疗组，斑块面积与厚度发生缩小，泡沫细胞减少。尤其在其中一组试验中，动脉粥样损伤坏疽的内含物发生减少。普罗布考治疗动物的主动脉斑块组成主要是平滑肌细胞和致密细胞间纤维结构。此外，普罗布考治疗组“典型”斑块还具有另外一个特征，其斑块通常缺少合生的坏疽核。与未治疗组相比，免疫组织化学测定普罗布考治疗组细胞内载脂蛋白B含量减少。试验证实了普罗布考在WHHL家兔中的抗动脉粥样硬化作用。另外普罗布考使动脉粥样硬化损伤发生改变，这种改变可能是由于普罗布考对斑块成分的直接抗氧化作用引起的。
Watanabe heritable hyperlipidaemic (WHHL)-rabbits develop premature atherosclerosis due to an inborn defect of the low-density lipoprotein (LDL) receptor causing severe hypercholesterolaemia. Probucol, which possesses a lipid lowering and an antioxidative potency, has been shown to reduce the extent of atherosclerotic disease in this animal. The object of the present study was the detailed analysis of the cellular and non-cellular composition of atherosclerotic lesions in WHHL-rabbits treated with probucol when compared with untreated controls.
In two independent sets of experiments, each consisting of one litter, a total number of 5 animals was fed a diet containing 1% (w/w) probucol. Four animals served as controls and 2 animals were sacrificed before treatment (at 2 and 4 months of age, respectively) to define the baseline level of the atherosclerotic disease. Morphometric analysis was employed in order to determine plaque area macroscopically by planimetry and plaque thickness and composition histologically, in 30 cross-sections of the aorta of each animal. In the group treated with probucol, a diminution of plaque area and thickness, as well as a decrease of foam cell and--especially in one experiment--necrotic content of atherosclerotic lesions, was observed. Plaques from aortas of animals treated with probucol consisted predominantly of smooth muscle cells and compact intercellular fibrous structures. Furthermore, as an additional characteristic feature of the "typical" probucol plaque, they usually lacked confluent necrotic cores. In comparison with untreated animals, there was also a decrease in intracellular apolipoprotein B (apo B) as determined by immunohistochemistry. These data confirm the antiatherosclerotic potency of probucol in the WHHL-rabbit. Moreover, it was demonstrated that there is a different type of atherosclerosis present in the group treated with probucol. The mechanism behind these shifts may be based on the antioxidative property as well as on direct effects of probucol on cellular plaque components.
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