载脂蛋白E基因敲除小鼠动脉粥样硬化斑块中血小板因子4和Toll样受体2的表达
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湖南省科技项目(06C692)资助


Platelet Factor 4 and Toll-Like Receptor 2 are Expressed in Atherosclerotic Plaques of Apolipoprotein E~(-/-)Mice
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    摘要:

    目的观察高脂饲养的载脂蛋白E基因敲除小鼠动脉粥样硬化斑块表达Toll样受体2和血小板因子4的情况,探讨血小板因子4对内皮细胞Toll样受体2表达的影响。方法高脂饲料喂养载脂蛋白E基因敲除小鼠12周,建立动脉粥样硬化模型。安乐死处死动物,原位灌流固定,取主动脉于10%中性缓冲福尔马林中固定,石蜡包埋连续切片,HE染色观察动脉粥样硬化斑块形态,免疫组织化学检测斑块中Toll样受体2和血小板因子4的表达。结果载脂蛋白E基因敲除小鼠血脂水平明显增高,主动脉HE染色可见态动脉粥样硬化病变。在载脂蛋白E基因敲除小鼠主动脉富含脂质斑块中Toll样受体2表达上调,其中血管内皮细胞、巨噬细胞表达Toll样受体2明显增多。载脂蛋白E基因敲除小鼠主动脉斑块中也发现有血小板因子4表达,主要在内皮细胞和动脉粥样硬化斑块肩部。结论1.载脂蛋白E基因敲除小鼠粥样斑块中Toll样受体2表达上调,并且Toll样受体2主要表达在粥样斑块的内皮细胞和巨噬细胞上。2.载脂蛋白E基因敲除小鼠动脉粥样硬化斑块中可见血小板因子4表达。

    Abstract:

    Aim To investigate a potential role of Toll-like receptor 2(TLR2) and platelet factor 4(PF4) in atherosclerosis,We assessed their expression in murine atherosclerotic plaques.Methods Twenty apolipoprotein E-/-mice at the age of 12 weeks were fed by high-fat diet,ten C57BL/6 mice at the age of 8 weeks were fed by standard laboratory chow for 12 weeks,then all of the animal were euthanized.Blood was sampled from the eye,the serum lipids was enzymatically detected.The thoracic and abdominalis aorta was fixed by in situ liquid flow.Thoracic aorta was fix in 10% formalin,paraffin imbedding,serial sections,and HE staining.Aortic lesions of high-fat diet-fed apolipoprotein E-/-mice were examined for TLR2 and PF4 expression by immunohistochemistry.Results Aortic atherosclerotic lesions in all apolipoprotein E-/-mice expressed TLR2,whereas aortic tissue obtained from control C57BL/6J mice showed no TLR2 expression.Serial sections immunostaining showed TLR2 localizing with macrophages and endothelial cells in murine atherosclerotic lesions.Furthermore,PF4 expression in murine atherosclerotic plaques were also observed.Conclusions TLR2 is expressed by macrophages and endothelial cells in murine atherosclerotic lesions,and we find that PF4 is also expressed in the plaques.They may play a role to enhance and sustain the innate immue and inflammatory responses.

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金海燕,彭茜,顾洪丰,唐雅玲,周浩,孙慧,杨永宗.载脂蛋白E基因敲除小鼠动脉粥样硬化斑块中血小板因子4和Toll样受体2的表达[J].中国动脉硬化杂志,2007,15(6):423~426.

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  • 收稿日期:2007-05-08
  • 最后修改日期:2007-06-11
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