氟伐他汀对巨细胞病毒感染后载脂蛋白E基因敲除小鼠动脉硬化的影响

目的 探讨巨细胞病毒（Cytomegalovirus）与动脉粥样硬化（Atherosclerosis,AS）形成的相关性及氟伐他汀对其的影响.方法 以载脂蛋白E基因缺陷（Apolipoprotein-E Knockout,apoE-/-）小鼠为研究对象,给予低剂量小鼠巨细胞病毒（Murine Cytomegalovirus,MCMV）,观察动脉粥样硬化病变的变化.并在氟伐他汀的干预下,观察病毒感染对AS的影响,以探讨MCMV在动脉粥样硬化形成及发展过程中所起的作用.结果 研究显示在慢性潜伏感染阶段,MCMV感染明显加重apoE-/-小鼠动脉粥样硬化病变面积;小鼠动脉壁中没有MCMV mRNA的表达;血浆MCMV抗体水平、唾液腺MCMV DNA含量和动脉粥样硬化病变程度没有相关性.氟伐他汀干预后,MCMV感染组与未感染组在AS病变的面积、数目、内膜/中膜比值方面的显著性差异消失.结论 在慢性潜伏感染阶段,MCMV感染可以明显加重apoE-/-小鼠主动脉AS病变,但在血管壁局部并无MCMV活动性感染的证据.氟伐他汀可以改善MCMV感染后apoE-/-小鼠的AS病变进程.但这种作用并不是通过减少病毒量来实现的.

Fluvastatin's effect on atherogenesis in apolipoprotein-E knockout mice infected by cytomegalovirus

Objective The goal of this study was to investigate whether murine cytomegalovirus (MCMV) is able to exacerbate the atherosclerotic process in apolipoprotein E knockout (apoE-/-) mice,and the effect of fluvastatin on the atherogenesis. Methods The apoE -/- mice kept on a west diet were given low dosage of MCMV. At 14,18 and 24 weeks post infection, AS lesion were measured on aorta. The fluvastatin was administered,and AS lesion were measured accordingly above. Results We observed that in the chronic phase of the infection, AS lesion area was significantly increased. MCMV gB mRNA was not amplified by real-time PCR from the arterial wall. The IgG antibody level of MCMV in blood plasma and the content of virus DNA in salivary gland were not correlated with AS lesions. After the administration of fluvastatin, there was no significant difference of AS lesions between MCMV infected group and mockinfected group. Conclusion MCMV may aggravate the AS lesion in apoE -/- mice in the chronic phase of infection, and promote more severe type of AS lesions. But it might not be the direct effects of mechanism of MCMV on the local lesion of AS. Fluvastatin could meliorate the progression of AS after MCMV infection,but this was not accomplished by decreasing MCMV duplication.