动脉粥样硬化动物模型筛选  

The selection of animal model for the study of atherosclerosis

作　　者：田光晶 马丛丛[1] 许继取[1] 

机构地区：[1]中国农业科学院油料作物研究所油料脂质化学与营养湖北省重点实验室,湖北武汉430062

出　　处：《中国食品卫生杂志》2017年第1期26-31,共6页Chinese Journal of Food Hygiene

基　　金：国家自然科学基金(NSFC-31171681);现代农业产业技术体系胡麻体系(CARS-17);中国农业科学院科技创新工程(CAAS-ASTIP-2013-OCRI)

摘　　要：目的以SD大鼠和ApoE基因敲除(ApoE^(-/-))小鼠为背景建立4种动脉粥样硬化(AS)模型,通过血浆脂质、炎症水平和病理学检测,筛选出AS研究的最佳动物模型。方法 8周龄的雄性健康SD大鼠60只,随机分成正常组(对照组1)、高脂组(模型组1)和高脂+维生素D_3组(模型组2);60只8周龄雄性C57BL/6小鼠,其中20只为野生型小鼠(对照组2)、40只为ApoE^(-/-)小鼠,随机分为正常基础饲料喂养组(模型组3)和高脂饲料喂养组(模型组4);6个月后观察体质量变化,检测血浆脂质和炎症水平,分离主动脉进行油红O和苏木精-伊红(HE)染色。结果与对照组1相比,模型组1和模型组2大鼠的血浆总胆固醇(TC)、白介素6(IL-6)和C反应蛋白(CRP)水平明显升高,差异有统计学意义(P<0.05),但是甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)没有明显变化,差异无统计学意义(P>0.05),而且模型组1和模型组2大鼠均未能产生AS斑块和AS的前期表现。另外,与对照组2相比,模型组3和模型组4小鼠血浆TC、TG和LDL-C以及炎症因子IL-6和CRP水平均明显升高,差异有统计学意义(P<0.05),并且其血浆TC、LDL-C、IL-6和CRP水平明显高于模型组3,差异有统计学意义(P<0.05)。此外,模型组4小鼠血浆HDL-C水平明显降低,差异有统计学意义(P<0.05),但是模型组3仅有部分脂质沉积和AS斑块出现,而模型组4表现为典型的AS特点。结论以模型组1和模型组2方法建立的大鼠AS模型不适合作为AS研究的对象;模型组3仅出现部分AS病理特点,而模型组4则发展为典型的AS病理特点,较为适合作为AS研究的对象。Objective In this study,four kinds of atherosclerotic models with SD rats and ApoE-（- /-） mice were established to select the best animal model for atherosclerosis. Methods Sixty male SD rats were randomly divided into three groups： the first group was fed on normal diets as control group; the second group was fed on high cholesterol diets as model 1 group; the third group was injected with a single dose of vitamin D_3 and fed on high fat diet,which was model 2group. Sixty C57 BL /6 male mice including 20 wild type mice and 40 ApoE-（- /-） mice which was divided into normal diet fed group as model 3 and high fat diet group as model 4. After 6 months,plasma lipids and inflammatory factors were detected,and the aorta was separated for oil red O and hematoxylin-eosin（ HE） staining. Results Compared with the normal group,plasma total cholesterol（ TC）,interleukin 6（ IL-6） and C reactive protein（ CRP） levels were significantly elevated（ P 0. 05）. But there＇s no difference between the three groups in plasma triglyceride（ TG）,low density lipoprotein cholesterol（ LDL-C） and high density lipoprotein cholesterol（ HDL-C） levels（ P 0. 05）,and both of the two models didn＇t have atherosclerotic plaques and the characteristics of the early stages of atherosclerosis. In addition,compared with the normal group,plasma TC,TG,LDL-C,IL-6 and CRP levels of model 3 and model 4 were significantly elevated（ P 0. 05）,and were significantly higher in model 4 than model 3（ P 0. 05）. But plasma HDL-C levels of model 4 were significantly reduced（ P 0. 05）. Oil red O and HE staining showed that model 3 only had lipid deposition and small atherosclerotic plaques in aortic arch; but the model 4 had developed typical characteristics of atherosclerosis.Conclusion Both the two models of SD rats established with high cholesterol diets and high cholesterol diets ＋ vitamin D_3 were not suitable for atherosclerosis research; Model 3 only had the early stage atherosclerotic characteristics; M

关 键 词：动脉粥样硬化 动物模型 大鼠 小鼠 

分 类 号：R543.5[医药卫生—心血管疾病] R-332[医药卫生—内科学]