巨细胞病毒感染的载脂蛋白E基因敲除小鼠动脉粥样硬化发生的可能机制
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国家自然科学基金(30571741);教育部新世纪优秀人才计划(NCET-06-0354);国家973项目(2007CB512003)


The Mechanism of Murine Cytomegalovirus Infection Contributing to Atherogenesis in Apolipoprotein E Knockout Mice
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    摘要:

    目的研究巨细胞病毒感染引起的免疫损伤导致动脉粥样硬化发生的可能机制。方法载脂蛋白E基因敲除的8周龄C57BL/6雌性小鼠,随机分成对照组、高脂饮食组、鼠巨细胞病毒感染组和高脂饮食+鼠巨细胞病毒感染组。在不同时间段分别处死小鼠,截取主动脉,利用逆转录聚合酶链反应、免疫组织化学等方法检测主动脉单核细胞趋化因子1、生长相关癌基因α、Fractalkine和调节活化正常T细胞表达与分泌的趋化因子的表达。结果第8周时,巨细胞病毒感染后可显著提高生长相关癌基因α在主动脉的表达,并可诱导Fractalkine、活化正常T细胞表达与分泌的趋化因子和单核细胞趋化因子1的表达,而在高脂饮食+巨细胞病毒感染的小鼠主动脉组织中,Fractalkine的表达较其它组明显升高。第12周时,高脂饮食+巨细胞病毒感染组中Fractalkine和活化正常T细胞表达与分泌的趋化因子和单核细胞趋化因子1的表达较其它组更高些。免疫组织化学结果发现,高脂饮食后,生长相关癌基因α、Fractalkine和单核细胞趋化因子1的表达均有明显升高,但Fractalkine的表达较局限,单核细胞趋化因子1和生长相关癌基因α在整个血管壁都存在,但以内膜较高。单纯巨细胞病毒感染组与高脂饮食组相似,可诱导单核细胞趋化因子1、生长相关癌基因α和Fractalkine的表达,但不同的是Fractalkine的表达广泛存在。而高脂饮食+巨细胞病毒感染组单核细胞趋化因子1、生长相关癌基因α和Fractalkine表达的升高更为明显,尤其是斑块部位。结论巨细胞病毒感染后通过调节趋化因子表达水平的改变,从而促进炎症细胞的迁移,促进动脉粥样硬化的发生。

    Abstract:

    Aim To study the immunologic injury mechanism of atherogenesis by murine cytomegalovirus(MCMV) infection. Methods Animal model of atherosclerosis(C57BL/6) with apolipoprotein E knockout mice were randomized to four groups: control group,hypercholesterol diet group,MCMV infection group,MCMV infection add hypercholesterol diet group,respectively.Mice from each group were sacrificed in different period.Portions of aortas were kept in-80℃.The expression of monocyte chemoattractant protein-1(MCP-1),growth-related oncogene-α(GRO-α),fractalkine(FKN) and regulated activation normal T cell expressed and secreted(RANTES) in aortas were detected by RT-PCR and immunohistochemistry. Results In the 8th week,the expression of GRO-α in aorta tissues was significant by CMV infection,and the expression of FKN,RANTES and MCP-1 was induced.The expression of FKN was more significant in MCMV infection add hypercholesterol diet group than other groups.In the 12th week,the expression of FKN and RANTES was marked than others.Immunohistochemistry staining also showed that the expression of MCP-1,GRO-α and FKN was enhanced in atherosclerotic lesion,but expression of FKN was variable,and correlated with the atherosclerotic plaque. Conclusion MCMV infection could contribute to atherogenesis by inducing the expression of chemokines and enhance the migration of inflammatory cells.

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陈瑞珍,熊思东,许从峰,杨英珍,邹云增,葛均波,陈灏珠.巨细胞病毒感染的载脂蛋白E基因敲除小鼠动脉粥样硬化发生的可能机制[J].中国动脉硬化杂志,2008,16(8):589~592.

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  • 收稿日期:2008-05-05
  • 最后修改日期:2008-07-29
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