Survival and cardiovascular pathology of heterozygous Watanabe heritable hyperlipidaemic rabbits treated with pravastatin and probucol on a low-cholesterol (0.03%)-enriched diet

    本研究的目的是考察普伐他汀与普罗布考联合用药对低胆固醇营养饮食饲养的杂合型WHHL家兔存活及其心血管病理学的影响。单独用药普法他汀的疗效优于联合治疗。接受普法他汀治疗和营养饮食饲养的动物（verum组，n=6）中，平均总血清胆固醇水平在5 mg/kg普法他汀和联合用药时均保持下降趋势。其存活时间延长（平均45 vs 25个月），与对照组相比（n=8）,冠脉粥样硬化纤维性更强，其阻塞程度减小。相对斑块体积衡量大动脉损伤程度，各组中与存活时间均无联系。然而，与同龄对照组动物相比，verum组动物的动脉斑块组成与结构不同，与巨噬细胞分化的泡沫细胞含量相关性较小，与细胞间质的含量有较大关联。其斑块的纤维帽较厚，属于严重程度较轻类型的斑块。数据显示降脂与抗氧化联合治疗能有效延长杂合型WHHL家兔的存活时间，表明是由减轻冠脉粥样硬化和动物模型中更稳定的动脉粥样硬化类型引起的。

    This study was aimed at determining the effects of a combined pravastatin and probucol regimen on survival and       vascular pathology of heterozygous Watanabe heritable hyperlipidaemic(WHHL) rabbits fed a low-cholesterol(0.03%)-enriched diet. Pravastatin monotherapy preceded the combined treatment. In animals receiving pravastatin and the enriched diet    (verum组; n = 6), mean total serum cholesterol levels were consistently lowered at a dosage of 5 mg/kg pravastatin and   with the combined treatment. Survival was increased (median 45 vs 25 months), while coronary atherosclerosis was less    obstructive and altered to a more fibrous type than in controls(n = 8).The extent of aortic lesions,as determined by the relative plaque volume, was not related to survival in either group. However, aortic plaque types in verum group animals revealed less severe stages with a different composition and architecture, with a lower relative content of   macrophage-derived foam cells and necrosis and a higher relative content of extracellular matrix.

    There was also a thicker fibrous cap than in control animals of similar age. Our data reveal a beneficial effect on  survival of heterozygous WHHL rabbits when lipid-lowering and antioxidative treatment are combined.This appears to be due both to reduced coronary atherosclerosis and to a different, more stable type of atherosclerotic disease in this animal  model.