Buja L M, Kita T, Goldstein J L, Watanabe Y, Brown M S
Arteriosclerosis. 1983 Jan-Feb;3(1):87-101. doi: 10.1161/01.atv.3.1.87.
This report describes the features of developing atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of human familial hypercholesterolemia. Observations were made in 18 homozygous WHHL rabbits, aged 4 days to 15 months, fed standard rabbit chow; seven control New Zealand white rabbits fed a similar diet, and four New Zealand white rabbits fed rabbit chow containing 2% cholesterol and 10% corn oil for 2 weeks. The WHHL rabbits showed evidence of progressive disease of the aorta with accumulation of strongly birefringent lipid in intimal lesions, including fatty streaks, raised foam cell lesions, and plaques (atheromas), as well as in the media. As seen by electron microscopy, the cellular population of the intimal lesions consisted predominantly of smooth muscle cells with lipid deposits and lipid-laden foam cells. Lipid deposits occurred as cytoplasmic neutral lipid droplets and as multilamellar bodies. In addition to advanced atherosclerosis of the aorta, a 15-month-old WHHL rabbit also had focal coronary atherosclerosis and subcutaneous xanthomas. The New Zealand white rabbits fed a high cholesterol and fat diet for 2 weeks showed early intimal lipid accumulation in the aorta and prominent lipid accumulation in hepatocytes and macrophages of the liver and spleen. New Zealand white rabbits fed the standard rabbit chow had no abnormal lipid deposits. In contrast to the cholesterol-fed rabbits, WHHL rabbits had only mild lipid accumulation in other tissues. Thus, many similarities exist between atherosclerotic disease in the WHHL rabbit and in man. This study shows that the WHHL rabbit is a good model of familial hypercholesterolemia.
本报告描述了渡边遗传性高脂血症（WHHL）兔（一种人类家族性高胆固醇血症的动物模型）动脉粥样硬化发展的特征。对18只年龄在4天至15个月的纯合WHHL兔进行观察，这些兔子喂食标准兔粮；7只对照新西兰白兔喂食类似饮食，还有4只新西兰白兔喂食含2%胆固醇和10%玉米油的兔粮2周。WHHL兔显示出主动脉渐进性病变的证据，在内膜病变（包括脂纹、隆起的泡沫细胞病变和斑块（动脉粥样瘤））以及中膜中积累了强双折射脂质。通过电子显微镜观察，内膜病变的细胞群体主要由有脂质沉积的平滑肌细胞和充满脂质的泡沫细胞组成。脂质沉积表现为细胞质中性脂质滴和多层体。除了主动脉的晚期动脉粥样硬化外，一只15个月大的WHHL兔还患有局灶性冠状动脉粥样硬化和皮下黄色瘤。喂食高胆固醇和高脂肪饮食2周的新西兰白兔在主动脉内膜出现早期脂质积累，在肝脏和脾脏的肝细胞和巨噬细胞中脂质积累显著。喂食标准兔粮的新西兰白兔没有异常脂质沉积。与喂食胆固醇的兔子相比，WHHL兔在其他组织中只有轻度脂质积累。因此，WHHL兔的动脉粥样硬化疾病与人类有许多相似之处。本研究表明，WHHL兔是家族性高胆固醇血症的良好模型。
