载脂蛋白E基因敲除小鼠动脉粥样硬化病变进展过程中循环单核细胞亚群和斑块内增殖巨噬细胞的动态变化
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国家自然科学基金(81170238);武警后勤学院院级课题(FYM201104,WHM201218)


The Dynamic Profile of Circulating Monocyte Subsets and Intraplaque Proliferating Macrophages During the Development of Atherosclerostic Lesion in ApoE Knockout Mice
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    摘要:

    目的 观察载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化病变进展过程中循环单核细胞亚群(Ly6GCD11bLyChi和Ly6GCD11bLy6Clo)比例和斑块内局部增殖巨噬细胞密度的动态变化。方法 40只ApoE-/-小鼠随机分为正常饮食组和高脂饮食组,分别于饮食干预后第2周末、第4周末、第6周末和第8周末处死部分动物,油红O染色检测主动脉根部动脉粥样硬化斑块面积,免疫荧光染色和共聚焦显微镜成像检测斑块内的巨噬细胞和增殖巨噬细胞(F4/80和Ki67双阳性细胞),流式细胞术分析循环单核细胞亚群比例。结果 随着高脂饮食时间的增加主动脉动脉粥样硬化病变逐渐加重;动脉斑块中总巨噬细胞和增殖巨噬细胞密度在高脂饮食后进行性升高,并于第4周末达到高峰;巨噬细胞与增殖巨噬细胞密度百分比在高脂饮食后进行性升高,并于第6周末达到高峰;随着高脂饮食时间的增加Ly6GCD11bLyChi单核细胞亚群比例逐渐增大。结论 在ApoE-/-动脉粥样硬化模型发展过程中,循环Ly6GCD11bLyChi单核细胞呈递增趋势,增殖巨噬细胞密度在第4周达到平台期。

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    Aim To detect the development of monocytes(Ly6GCD11bLy6Chi and Ly6GCD11bLy6Clo)and proliferating macrophage in atherosclerosis of ApoE―/― mice. Methods We randomly assigned 40 ApoE-/- mice into high-fat diet or normal chow diet group, which were sacrificed at the end of weeks 2, 4, 6 and 8. Lipids of aortic sinus were stained with oil red O. The macrophage and proliferating macrophage(F4/80 and Ki67 double positive cells)in plaque were detected by immunofluorescence staining and confocal microscopy. Flow cytometry methods were used to analyze the proportions of circulationg monocyte subsets. Results In the formation progress of atherosclerosis, aortic atherosclerosis gradually aggravated with high-fat diet over time. The total macrophages and proliferation macrophage density showed an increasing trend before the first four weeks with high-fat diet, which reached a peak at the fourth week. Before the first six weeks with high-fat diet, the percentage of proliferating macrophage and macrophages density were gradually increased and reached a peak at the sixth week. The proportions of cycle Ly6Chi monocyte was increased with high-fat diet time passing. Conclusions In the development progress of atherosclerosis model, the proportions of circulating Ly6GCD11bLy6Chi monocyte subsets gradually aggravated with high-fat diet time passing and the increasing is consistent. Proliferating macrophage density reached a plateau at the first four weeks.

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李 宵,周 欣,姬文婕,李玉秀,赵季红,李玉明.载脂蛋白E基因敲除小鼠动脉粥样硬化病变进展过程中循环单核细胞亚群和斑块内增殖巨噬细胞的动态变化[J].中国动脉硬化杂志,2015,23(01):24~28.

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  • 收稿日期:2014-09-02
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