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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 To establish four models of atherosclerosis (AS) in SD rats and ApoE ~ (- / -) mice, and to screen out the effects of AS on plasma lipid, inflammation and pathology Study the best animal model. Methods Sixty male Sprague-Dawley (SD) rats of 8 weeks old were randomly divided into normal group (control group 1), high fat group (model group 1) and high fat + vitamin D 3 group (model group 2) C57BL / 6 mice, of which 20 were wild type mice (control group 2) and 40 were ApoE ~ (- / -) mice. They were randomly divided into normal basal diet group (model group 3) and high fat diet (Model group 4). After 6 months, the change of body weight was observed. The levels of plasma lipids and inflammation were measured. The aorta was separated for oil red O and hematoxylin-eosin (HE) staining. Results Compared with control group 1, the levels of total cholesterol (TC), interleukin 6 (IL-6) and C-reactive protein (CRP) in model group 1 and model group 2 were significantly increased (P <0.05), but TG, LDL-C and HDL-C had no significant difference (P> 0.05), and Both model group 1 and model group 2 rats failed to produce AS plaques and pre-AS manifestations. In addition, compared with control group 2, the levels of TC, TG and LDL-C, IL-6 and CRP in model group 3 and model 4 mice were significantly increased (P <0.05) , And the plasma levels of TC, LDL-C, IL-6 and CRP were significantly higher than those in model group 3 (P <0.05). In addition, the level of plasma HDL-C in model group 4 mice was significantly lower than that in model group 4 (P <0.05), but only partial lipid deposition and AS plaque appeared in model group 3, while model group 4 showed typical AS features. Conclusion The model of rat AS established by model group 1 and model group 2 is not suitable for the study of AS. Model 3 only shows part of pathological features of AS, while model group 4 develops typical pathological features of AS, which is more suitable for AS research object.