腱糖蛋白-C在载脂蛋白E基因敲除小鼠动脉粥样硬化斑块不同时期表达的变化

Dynamic Expressions of Tenascin-C at Different Phases of Atherosclerosis in ApoE^(-/-) Mice

目的:探讨腱糖蛋白-C(TN-C)在载脂蛋白E基因敲除(ApoE^(-/-))小鼠动脉粥样硬化斑块形成过程中不同时期表达的动态变化。方法:取雄性SPF级ApoE^(-/-)小鼠50只(模型组),高脂饲料喂养,建立小鼠动脉粥样硬化模型,雄性SPF级野生型C57BL/6小鼠50只为对照组,同样高脂饮食。分别于喂养4、8、16、24、32周时处死小鼠,检测血脂,显微镜观察斑块病理改变并进行定量分析,免疫组化方法检测动脉粥样硬化斑块内TN-C表达。结果:模型组小鼠总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平均高于对照组小鼠(P均<0.05)。随着造模时间的进展,模型组小鼠斑块面积及斑块面积/管腔面积比值不断增加,各时期比较差异均有统计学意义(P均<0.05)。模型组小鼠斑块内TN-C表达量随着动脉粥样硬化进展而增多,32周小鼠斑块内部TN-C表达升高最显著,高于8、16、24周小鼠(分别为0.49±0.07 vs 0.04±0.02、0.12±0.03、0.21±0.04,P<0.05)。结论:TN-C的表达量随着斑块进展不断增加,可能与动脉粥样硬化进展及斑块不稳定性有关。

Objective： To investigate the dynamic expressions of tenascin-C （TN-C） at different phases of atherosclerosis in ApoE^-/-mice. Methods： Our research included in 2 groups： ApoE^-/- group, n=50 SPF male mice with ApoE^-/- and Control group, n=50 wild male C57BL/6 mice. Atherosclerosis model was established by high fat diet in both groups. The mice were sacrificed at 4, 8, 16, 24 and 32 weeks, blood lipids were examined, pathologic changes of plaque were observed by microscope for quantitative analysis and TN-C expressions in atherosclerosis plaque were measured by immunohistochemistry. Results： Compared with Control group, ApoE^-/- group had elevated blood levels of total cholesterol （TC） and low density lipoprotein cholesterol （LDL-C）, both P〈0.05. In ApoE^-/- group, plaque area and the ratio of plaque area/lumen area were increasing upon prolonged modeling time, all P〈0.05; TN-C expressions were increasing by progress of atherosclerosis, the highest TN-C expression was found at 32 weeks of modeling （0.49±0.07） which was higher than it was at 8 weeks （0.04±0.02）, 16 weeks （0.12±0.03） and 24 weeks （0.21±0.04）, all P〈0.05. Conclusion： TN-C expression was increasing with plaque progress which might be related to the development of atherosclerosis and plaque instability.