Objective: To explore a modified method for constructing a mouse model of instable carotid plaque and provide the mouse model for simulating the development of human instable carotid plaque. Methods: Twenty-four low density lipoprotein receptor deficiency (LDLr-/-), C57BL/6, male mice were randomized into two groups according to computer-generated table, tandem constriction of carotid artery+ high cholesterol diet (tandem surgery group, n=12); sham surgery+ high cholesterol diet(sham surgery group, n=12). After 12 weeks of consecutive feeding, murine carotid artery were collected and analyzed by carotid ultrasound, pathological examination to assess the formation and stability of atherosclerotic plaque. Results: No statistical difference in body weight and blood lipid level between the two groups was observed (all P>0.05). After surgery, through ultrasound biomicroscopy, obvious stenosis at the two sites of tandem constriction and atherosclerotic plaque between the two sites were observed in tandem surgery group. By pathological examination, no plaque was formed in carotid artery in sham surgery group. The lipid area in the stable plaque of innominate artery in sham surgery group and the plaque of carotid artery in tandem surgery group were (4.8±0.6) ×10(4),(10.2±1.1)×10(4) μm(2), respectively. The difference was statistically significant between the two groups (t=12.023,P<0.001). In addition, the thickness of fibrous cap in the above groups were (122.4±17.8), (41.3±20.2) μm, respectively. The difference was statistically significant either (t=9.224, P<0.001). The region of necrotic core were (3.3±0.4)×10(4),(8.1±0.9)×10(4) μm(2).The difference was statistically significant as well (t=13.456, P<0.001). The percentage of macrophages in innominate artery of sham surgery group and in carotid artery of tandem surgery group were (20.8±5.2)%, (38.6±6.4)%, respectively.The percentage of vascular smooth muscle cells were (32.5±7.3)%,(21.2±5.1)%, respectively (t=6.114,3.585, all P<0.05). The results indicated that the plaque in tandem surgery group had severer inflammatory response. Conclusion: Through tandem constriction surgery upon carotid artery in LDL-/-mouse, instable carotid atherosclerotic plaque can be induced, which is less time-consuming, replicable and effective.
目的： 探讨一种改良后的小鼠颈动脉不稳定粥样硬化斑块模型构建方法，为模拟人的颈动脉不稳定斑块形成提供动物模型。 方法： 选择低密度脂蛋白受体敲除（LDLr-/-）的C57BL/6雄性小鼠24只，随机数字表法分为颈动脉串联结扎+高胆固醇饮食组（造模组，n=12）和假手术+高胆固醇饮食组（假手术组，n=12）。两组均连续进行12周喂养，而后对小鼠颈动脉进行取材，利用小动物颈动脉超声、病理形态观察等方法判断颈动脉斑块形成及稳定性情况。 结果： 两组小鼠体质量、血脂差异均无统计学意义（均P>0.05）。造模组小鼠术后颈动脉有明显狭窄形成，并在两端狭窄处之间的血管探测到有斑块形成。通过病理形态学观察，假手术组颈动脉未见斑块形成，假手术组头臂干动脉稳定斑块及造模组颈动脉斑块中脂质沉积面积分别为（4.8±0.6）×10(4)，（10.2±1.1）×10(4) μm(2)，差异有统计学意义（t=12.023，P<0.001）。另外两组斑块纤维帽厚度分别为（122.4±17.8）、（41.3±20.2）μm，差异有统计学意义（t=9.224，P<0.001）；两组坏死核心面积分别为（3.3±0.4）×10(4)、（8.1±0.9）×10(4) μm(2)，差异有统计学意义（t=13.456，P<0.001）。假手术组头臂干动脉稳定斑块及造模组颈动脉斑块中巨噬细胞占斑块中总细胞的比例分别为（20.8±5.2）%、（38.6±6.4）%，平滑肌细胞比例分别为（32.5±7.3）%、（21.2±5.1）%，差异均有统计学意义（t=6.114、3.585，均P<0.05），提示造模组斑块炎症反应更强烈。 结论： 将LDLr-/-小鼠进行颈动脉串联结扎手术用于不稳定颈动脉斑块构建具有周期短、模拟效果确切、可重复性强等优点。.
Keywords: Atherosclerosis; Mice; Models, animal; Stroke.