巨噬细胞及其相关因子在家兔不稳定斑块中的作用及其机制

Role and mechanism of macrophages and its related-factors in vulnerable plaque of rabbits

[目的]探讨巨噬细胞及其相关炎症因子在家兔不稳定斑块中的作用及其机制。[方法]高脂饲料喂养家兔2周,按随机数字表法随机分为假手术组和模型组,模型组球囊拉伤腹主动脉内皮,假手术组仅暴露动脉但不进行拉伤。术后10周以蝰蛇毒和组胺进行两次药物触发,第2次药物触发后24 h处死动物、取材。计数破裂斑块的数量。行免疫组织化学染色,确定斑块中巨噬细胞百分比。酶联免疫吸附法(ELISA)法检测相关炎症因子C反应蛋白(CRP)、单核细胞趋化因子-1(MCP-1)及肿瘤坏死因子-α(TNF-α)的水平。[结果]与假手术组比较,模型组斑块破裂数量明显增多、斑块面积较大,泡沫细胞数量较多,脂核较大,纤维帽较薄,炎细胞浸润较多。模型组粥样斑块内巨噬细胞浸润百分比、血清炎症相关因子CRP、MCP-1及TNF-α的水平均高于假手术组(P<0.01)。[结论]球囊损伤内皮细胞促进动脉粥样硬化的发生发展,巨噬细胞介导的炎症反应可能是不稳定斑块模型形成的重要机制。

[Objective] To investigate the role and the mechanism of macrophages and their related factors in the vulnerable plaque of rabbit. [Methods] Rabbits were fed with high-fat diet for two weeks. The rabbits were divided into two groups： the sham group and the model group. The model group received a balloon injury in its aorta abdominalis. The arteria cruralisin the sham group was exposed but the balloon was not inserted. The rabbits underwent a pharmacological triggering with Chinese Russell＇s viper venom and histamine at the end of 10th week after the surgery these animals were then killed. The ruptured plaque was counted. The percentage of macrophage in the plaque was calculated by immunohistochemical staining. The inflammatory factors, such as CRP, MCP-1 and TNF-α were detected by Elisa. [Results] Compared with sham group, in the model group there were significantly more ruptured plaque, larger plaque area, bigger lipid core, thinner fibrous cap, more foam cells and inflammatory cells. The percentage of macrophages in the plaque of model group was higher than that of sham group （P〈0.01）. Compared with the sham group, the inflammatory factors, such as CRP, MCP-1 and TNF-α in the model group were up-regulated evidently. [Conclusion] Balloon injury of endothelial cells can promote the development of atherosclerosis. The inflammatory reaction mediated by macrophages may be a important mechanism in the formation of vulnerable plaque.