ApoE基因敲除小鼠颈动脉斑块模型构建的研究

Establishment of carotid plaque model in ApoE gene knockout mice

目的探索一种快速建立小鼠颈动脉斑块模型的有效方法。方法将C57BL/6J种系ApoE基因敲除[ApoE(-/-)]雄性小鼠50只随机分为5组:A组为空白对照组,不进行手术干预,仅普通饲料喂养4周;B组为手术普食组,使用200μm硅胶管进行颈总动脉套管后普通饲料喂养4周;C组为单纯高脂组,不进行手术干预,高脂饲料喂养4周;D组为手术高脂组,进行手术干预后高脂饲料喂养4周;E组为基础数据组。每周监测小鼠体重、心率、血压;造模结束后心室取血进行血脂检测;取小鼠双侧颈总动脉进行苏木精-伊红染色、油红O染色观察颈总动脉斑块形成情况。结果A、B组小鼠总胆固醇含量较E组明显上升(P<0.05),但明显低于C、D组(P<0.05);A、B组小鼠甘油三酯含量较E组未见明显变化(P=0.207),但明显高于C、D组(P<0.05);A、B组小鼠高密度脂蛋白胆固醇含量较E组明显上升(P<0.05),也明显高于C、D组(P<0.05);A、B组小鼠低密度脂蛋白胆固醇含量较E组未见明显变化(P=0.298),但明显低于C、D组(P<0.05);A、B组小鼠颈动脉外径与C、D组相比未见明显变化(P=0.213),但都明显大于E组(P<0.05)。染色结果发现A、C组小鼠双侧颈总动脉均未形成明显的颈动脉斑块,B组有4只小鼠右侧颈总动脉内膜增厚,局部少量脂质沉积,D组有8只小鼠右侧颈总动脉形成进展型纤维粥样斑块,斑块局部有明显脂质沉积和泡沫细胞浸润。结论使用200μm硅胶管对C57BL/6J种系ApoE(-/-)小鼠进行颈总动脉套管后合并高脂喂养可以快速、有效地建立颈动脉粥样硬化斑块模型,是一种易于重复的高效造模方法。

Objective To explore an effective method for rapidly establishing a mouse model of carotid plaque.Methods Fifty male C57BL/6J ApoE gene knockout[ApoE(-/-)]mice were randomly divided into five groups.Group A were fed with ordinary feed only for 4 weeks and without surgical intervention.Group B were performed a common carotid cannula cuff by 200μm silicone,and fed with ordinary feed for 4 weeks.Group C were fed with high-fat diet for 4 weeks and without surgical intervention.Group D were performed a common carotid cannula cuff,and fed with high-fat diet for 4 weeks.Group E were the basic data group.The body weight,heart rate and blood pressure of the mice were monitored weekly.The blood samples of ventricle blood were taken for blood lipid detection.The bilateral common carotid arteries of the mice were used for HE and oil red staining,which was used to observe the formation of common carotid plaque.Results The content of total cholesterol in group A and B was significantly higher than that of E group(P<0.05),but significantly lower than that of group C and D(P<0.05).There was no significant difference of triglyceride content between group A,B and group E(P=0.207),but was significantly higher than that of group C and D(P<0.05).The content of high-density lipoprotein cholesterol in group A and B as significantly higher than that of group E(P<0.05),and also higher than that of group C and D(P<0.05).There was no significant difference of low-density lipoprotein cholesterol content between group A,B and group E(P=0.298),but was significantly lower than that of group C and D(P<0.05).There was no significant difference of carotid diameter between group A,B and group C,D(P=0.213),but they were significantly larger than group E(P<0.05).Staining showed that no obvious carotid plaques were formed in the bilateral common carotid arteries in groups A and C,four mice’s right common carotid intima were thickened and a small amount of local lipid deposition in group B,and eight mice’s right common carotid arteries developed progressive fibrous plaques with significant lipid deposition and foam cell infiltration in group D.Conclusion 200μm silicone cuff for common carotid cannula with high-fat diet for C57BL/6J ApoE(-/-)mice can establish a carotid atherosclerotic plaque model quickly and effectively,which is easy to repeat.