首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (2): 160-165.

• 神经病学专题 • 上一篇    下一篇

巨细胞病毒感染加重载脂蛋白E基因敲除小鼠动脉粥样硬化

易立1, 脱厚珍1*, 赵日光2, 王得新1, 冯子敬1   

  1. 1. 首都医科大学附属北京友谊医院神经内科;2. 天津市宝坻区人民医院神经内科
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-04-21 发布日期:2010-04-21
  • 通讯作者: 脱厚珍

Cytomegalovirus Infection Aggravates Atherogenesis in Apolipoprotein E Knockout Mice

YI Li1, TUO Hou-zhen1*, ZHAO Ri-guang2, WANG De-xin1, FENG Zi-jing1   

  1. 1. Department of Neurology, Beijing Friendship Hospital, Capital Medical University;2. Department of Neurology, Tianjin Baodi Hospital
  • Received:1900-01-01 Revised:1900-01-01 Online:2010-04-21 Published:2010-04-21
  • Contact: TUO Hou-zhen

摘要: 目的 本研究以载脂蛋白E基因敲除(apolipoprotein-E knockout,apoE-/-)小鼠为研究对象,给予低剂量的小鼠巨细胞病毒(murine cytomegalovirus,MCMV),以期了解在模拟人体内潜伏感染状态下病毒对动脉粥样硬化形态学方面的影响,以及凝集素样氧化型低密度脂蛋白受体-1(lectin-like ox-LDL receptor-1,LOX-1)基因的表达变化,以探讨MCMV在动脉粥样硬化形成及发展过程中所起的作用。方法 采用随机数字表法将32只高脂饮食apoE-/-小鼠随机分为2组,其中1组经腹腔感染MCMV,分别在感染后14周、18周和24周截取主动脉;另1组不感染MCMV。通过HE染色观察2组动物主动脉粥样硬化病变的面积、数目、分级和内膜/中膜比值,实时定量PCR(real-time PCR)检测动脉壁和唾液腺中的MCMV含量以及LOX-1基因表达量的变化。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;但随感染时间的延长,该作用逐步减弱。小鼠动脉壁中没有MCMV mRNA的表达。血浆MCMV抗体含量、唾液腺MCMV DNA含量和动脉粥样硬化病变程度没有相关性。感染后14周,病毒组LOX-1 mRNA含量较对照组明显增高。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,并使重度AS病变提前出现,但在血管壁局部并无MCMV活动性感染的证据。MCMV感染后可增加动脉壁LOX-1基因表达,LOX-1的高表达可能是MCMV加重动脉粥样硬化形成的途径之一。

关键词: 小鼠巨细胞病毒, 动脉粥样硬化, apoE-/-小鼠, 凝集素样氧化型低密度脂蛋白受体-1

Abstract: Objective Atherosclerosis plays an important role in the brain stroke. Cytomegalovirus(CMV) infection has been associated with atherosclerotic process. The goal of this study was to investigate whether murine cytomegalovirus(MCMV) infection is able to exacerbate the atherosclerotic process in atherosclerosis-susceptible mice. Methods The apolipoprotein E knockout(apoE-/-) mice kept on high fat feed were given low dosage of MCMV to mimic the latent stage of CMV infection in human. At 14. 18 and 24 weeks post infection, the area, number and type of atherosclerotic lesion and the intima/median ratio(I/M) were measured on aorta. The results were determined by means of a microscope coupled to a computer-assisted morphometry system. And the level of lectin-like ox-LDL receptor-1(LOX-1) mRNA in the arterial wall was measured by real-time PCR. The mechanism of MCMV infection on AS formation was investigated. Results In the chronic phase of the infection the area of lesion was significantly increased after MCMV infection in the apoE-/- mice. But with the increase of post-infection period, the role of MCMV on atherosclerosis reduced gradually. MCMV gB mRNA was not amplified by real-time PCR from the arterial wall. The specific IgG antibody level of MCMV in blood plasma and the content of virus DNA in salivary gland were not correlated with atherosclerotic lesions. At 14 weeks post infection, LOX-1 mRNA in arterial wall increased significantly in MCMV infected group. Conclusion MCMV may aggravate the atherosclerotic lesion in apoE-/- mice in the chronic phase of infection, and promote more severe type of atherosclerotic lesions. But it might not be the direct effects of MCMV on the local lesion of atherosclerosis. The increased expression of LOX-1 in arterial wall may be the mechanism through which MCMV aggravate the atherosclerosis.

Key words: murine cytomegalovirus, atherosclerosis, apolipoproteinE knockout mice, lectin ike ox DL receptor-1

中图分类号: