构建不同周龄载脂蛋白E基因敲除动脉粥样硬化模型小鼠血脂和病理学观察

Serum lipid levels and pathological observation of apolipoprotein E knockout mice with atherosclerosis at different weeks of age

背景:载脂蛋白E基因敲除小鼠形成的动脉粥样硬化病变与人类全身动脉粥样硬化好发处相近,是目前建立动脉粥样硬化理想的动物模型。目的:研究载脂蛋白E基因敲除小鼠不同周龄动脉粥样硬化的病理进程,探讨不同饮食对载脂蛋白E基因敲除小鼠动脉粥样硬化发生发展的影响。方法:将8周龄雄性载脂蛋白E基因敲除小鼠,随机分为2组,分别给予高脂饮食和普通饮食喂养8,12,16,20,24周。结果与结论:血清学指标检测显示,不同周龄的高脂饮食组血清中总胆固醇、三酰甘油和低密度脂蛋白胆固醇水平显著高于普通饮食组(P<0.05),呈时间依赖性。大体和冰冻切片油红O染色结果显示,高脂饮食组动脉粥样硬化管腔斑块面积显著高于普通饮食组(P<0.05),呈时间依赖性,此时两组各周龄小鼠管腔斑块面积相比均有显著性意义(P<0.05),小鼠在高脂饮食16周时主动脉可见明显的脂质斑块。结果表明,实验成功构建了载脂蛋白E基因敲除动脉粥样硬化模型小鼠,此模型形成脂质条纹和纤维增生病变的时间较普通饮食组更快。

BACKGROUND：The formation of atherosclerotic lesions in apolipoprotein E knockout mice is similar to that of human systemic atherosclerosis, and apolipoprotein E knockout mice are ideal animals for current establishment of atherosclerosis models. OBJECTIVE：To research the pathological process of atherosclerosis in apolipoprotein E knockout mice aged different weeks, and to explore the effect of different diets on the occurrence and development of atherosclerosis in apolipoprotein E knockout mice. METHODS：Male apolipoprotein E knockout mice aged 8 weeks old were randomly divided into two groups, and fed with high fat diet and normal diet, respectively, for 8, 12, 16, 20, and 24 weeks. RESULTS AND CONCLUSION：Serological detection revealed that serum total cholesterol, triglycerides and low density lipoprotein levels were significantly higher in different weeks of mice of high fat diet group than in the normal diet group （P〈0.05）, in a time-dependent manner. Gross and frozen oil red O staining showed that atherosclerotic plaque area of lumen was significantly larger in the high fat diet group than in the normal diet group （P〈0.05）, in a time-dependent manner. At this time, significant differences in plaque area of lumen at each week were detected＆nbsp;between both groups （P〈0.05）. Apparent lipid plaque was visible in aorta at 16 weeks of high fat diet in mice. Results demonstrated that apolipoprotein E knockout mice of atherosclerosis were successful y established. The formation of lipid streaks and fiber hyperplasia was faster in high fat diet group than in the normal diet group.