ApoE基因缺失幼龄小鼠动脉粥样硬化相关基因的时序表达研究

Sequential Expression of Atherosclerosis Related Genes in Young ApoE Gene Deficient Mice

利用RT-PCR技术检测apoE基因缺失(apoE-/-)小鼠在1、2和3月龄3个年龄段主动脉以及14天、1、2和3月龄4个年龄段肝脏中动脉粥样硬化(atherosclerosis,AS)重要相关基因的时序表达特点,并通过血清生化检测结合主动脉根部病理形态学特征的分析,探讨AS重要相关基因时序表达特点与AS早期病变的关系.在主动脉检测的9条AS相关基因中,apoE-/-与野生型(WT)小鼠相比,1、2和3月龄时IL-1β的mRNA表达水平均显著上调.1月龄时VCAM-1、IκB和TGF-β,2月龄时PDGF-α和CD36,3月龄时TNF-α和MMP2的mRNA表达水平均显著上调,其他年龄段无显著变化.在肝脏检测的2条AS相关基因中,C反应蛋白(CRP)的mRNA表达水平在14天到2月龄时无显著变化,3月龄时显著上调.NF-κB在各年龄段apoE-/-小鼠主动脉和肝脏中的基因表达量与同龄WT小鼠相比均无显著差异.不同年龄段的apoE-/-小鼠血清TC、TG和LDL-C水平均明显高于同龄WT小鼠.2月龄apoE-/-小鼠主动脉内膜出现散在的脂质沉积,并随年龄增长逐渐加重.上述结果显示,时序表达上调的AS重要相关基因构成了以NF-κB为核心的复杂调控网络,它们之间相互作用,共同参与慢性炎症过程,在apoE-/-小鼠AS的早期发生发展中发挥重要作用.

RT-PCR assays have been used to analyze expression patterns of atherosclerosis related genes in aorta from 1 to 3-month and liver from 14-day to 3-month old of atherosclerotic model, young apoE deficient （apoE^-/-） mice in normal chow diet. The level of plasma lipids was also analyzed. Combined with the pathomorphological characteristics of the aortic root, the sequential expression characteristics of atherosclerosis related genes in the early stage of the atherosclerosis were studied. ApoE^-/- mice compared with WT mice, the genes detected in the aorta, the expressions of VCAM-1, IκB and TGF-β in 1-month old of the apoE ^-/- mice were prominently up-regulated; while the expression of PDGF-α and CD36 were significantly up-regulated in 2-month old, the mRNA levels of TNF-α and MMP2 in 3-month old mice were prominently up-regulated, and IL-1β was significantly up-regulated from 1 to 3-month old. The genes detected in the liver, the mRNA level of CRP was significantly up-regulated at 3-month old of the apoE^-/- mice. The mRNA level of NF-κB had no significant change at different ages in the aorta and liver in the two types of mice. Serum TC, TG and LDL-C levels in different ages of apoE^-/- mice were significantly higher than those of WT mice. It appeared lipid deposition in the intima of aortic root in 2-month old apoE^-/- mice. With the increasing of age, the lesions became more serious. The results implied that the sequential and differential expression of genes related to atherosclerosis formed a complex regulatory network which NF-κB is the core, and the genes may interact with each other and play important roles in the early stages of atherosclerosis of young apoE^-/- mice.