Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate
Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate
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DOI：
10.1161/01.atv.19.8.1938
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发表时间：
1999-08-01
影响因子：
8.7
通讯作者：
Cybulsky, MI
中科院分区：
文献类型：
--
作者：
Lichtman, AH;Clinton, SK;Cybulsky, MI
过去对小鼠动脉粥样硬化的研究使用了补充胆固醇、脂质和胆酸钠的以普通食物为基础的饮食，以克服物种对病变形成的抵抗力。在LDL受体缺陷（LDLR-/-）小鼠的研究中常规使用类似的饮食。含胆酸盐饮食的非生理性质和潜在毒性导致推测这些小鼠的动脉粥样硬化形成可能不能准确反映人类疾病过程。我们设计了一种基于AIN-76A的半纯化饮食，可以以粉末、颗粒或液体形式喂养，并用于精确评估小鼠动脉粥样硬化中的饮食-遗传相互作用。将LDLR-/-小鼠随机分配至如下4种饮食（n = 6/饮食）中：1，对照，10%kcal脂质; 2，高脂肪（40%kcal），中等胆固醇（0.5%重量）; 3，高脂肪，高胆固醇（1.25%重量）;和4，高脂肪，高胆固醇和0.5%（wt/wt）胆酸钠。与对照组相比，所有补充维生素E的小鼠在喂养6或12周后，空腹血清胆固醇均升高（P
Past studies of atherosclerosis in mice have used chow-based diets supplemented with cholesterol, lipid, and sodium cholate to overcome species resistance to lesion formation. Similar diets have been routinely used in studies with LDL receptor-deficient (LDLR-/-) mice. The nonphysiological nature and potential toxicity of cholate-containing diets; have led to speculation that atherogenesis in these mice may not accurately reflect the human disease process. We have designed a semipurified AIN-76A-based diet that can be fed in powdered, pelleted, or liquid form and manipulated for the precise evaluation of diet-genetic interactions in murine atherosclerosis. LDLR-/- mice were randomly assigned among 4 diets (n=6/diet) as follows: 1, control, 10% kcal lipid; 2, high fat (40% kcal), moderate cholesterol (0.5% by weight); 3, high fat, high cholesterol (1.25% by weight); and 4, high fat, high cholesterol, and 0.5% (wt/wt) sodium cholate. Fasting serum cholesterol was increased in all choleslerol-supplemented mice compared with controls after 6 or 12 weeks of feeding (P