CHOLESTEROL-FED HETEROZYGOUS WATANABE HERITABLE HYPERLIPIDEMIC RABBITS - A NEW MODEL FOR ATHEROSCLEROSIS

CHOLESTEROL-FED HETEROZYGOUS WATANABE HERITABLE HYPERLIPIDEMIC RABBITS - A NEW MODEL FOR ATHEROSCLEROSIS
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DOI:
10.1016/0021-9150(89)90216-5
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发表时间:
1989-08-01
期刊:
影响因子:
5.3
通讯作者:
SWIFT, LL
SWIFT, LL
中科院分区:
医学2区
文献类型:
--
作者:
ATKINSON, JB;HOOVER, RL;SWIFT, LL

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Watanabe遗传性高脂血症(WHHL)纯合子兔被广泛用于动脉粥样硬化的研究,但WHHL杂合子兔却鲜有人关注。为了研究其作为动脉粥样硬化模型的潜力,对杂合子WHHL和新西兰白(NZW)兔分别饲喂含0%、0.5%和1.0%胆固醇的日粮。分别于0、4、8、12、16、24周测定血脂,12周、24周处死动物。饲喂胆固醇的WHHL杂合子在8周时血浆胆固醇水平显著高于NZW兔,但在其他时间无明显差异。高胆固醇饲养的WHHL杂合子兔的动脉粥样硬化斑块与NZW兔的不同之处在于WHHL有复杂的病变,包括坏死、胆固醇裂隙、纤维帽和钙化,与人类和纯合子WHHL兔相似。相比之下,新西兰兔的病变主要是泡沫细胞。杂合子WHHL兔血管外泡沫细胞沉积也较少。我们的结果表明,胆固醇喂养的杂合子WHHL兔可能为研究动脉粥样硬化的发病机制提供一个有前途的模型。
Homozygous Watanabe heritable hyerplipidemic (WHHL) rabbits are used widely to study atherosclerosis, but the WHHL heterozygous rabbit has received little attention. To study their potential as a model for atherosclerosis, heterozygous WHHL and New Zealand white (NZW) rabbits were fed diets containing 0%, 0.5% and 1.0% cholesterol. Plasma lipids were analyzed at 0, 4, 8, 12, 16 and 24 weeks, and animals were killed at 12 and 24 weeks. Plasma cholesterol levels were significantly higher in cholesterol-fed WHHL heterozygotes at 8 weeks compared with NZW rabbits, but no differences were apparent at other times. Atherosclerotic plaques in the aortas of cholesterol-fed WHHL heterozygous rabbits differed from those in NZW rabbits, in that the WHHL had complicated lesions with necrosis, cholesterol clefts, fibrous caps and calcification, similar to that found in humans and homozygous WHHL rabbits. In contrast, NZW rabbits had predominantly foam cell lesions. Heterozygous WHHL rabbits also had less extensive extravascular foam cell deposits. Our results suggest that the cholesterol-fed heterozygous WHHL rabbit may provide a promising model for studying the pathogenesis of atherosclerosis.