目的:采用DNA甲基化芯片技术探讨高脂饮食对Apo E-/-小鼠动脉粥样硬化模型全基因组DNA甲基化的影响。方法:30只雄性Apo E-/-小鼠随机分为正常组与高脂组,每组15只,正常组给予正常饲料喂养,高脂组给予高脂饲料喂养。16周后,测其血脂、血清同型半胱氨酸水平(Hcy)水平、血清DNA甲基化与血清DNA甲基化转移酶(DNMTs)水平;采用DNA甲基化芯片检测两组小鼠主动脉组织全基因组甲基化情况。结果:与正常组相比,高脂组小鼠血清CHOL、TG、LDL-C均显著升高,HDL-C显著下降;血清DNA甲基化水平与血清DNA甲基化转移酶(DNMTs)水平均显著升高。甲基化芯片结果显示:与正常组相比,高脂组主动脉全基因组中共有875个基因甲基化发生改变,差异具有统计学意义(P<0.05),其中高甲基化基因数目496,占总数56.69%;低甲基化基因数目379,占总数的43.31%。结论:高脂饲料可升高主动脉基因组甲基化水平,降低基因组的表达,可能是Apo E-/-小鼠容易形成动脉粥样硬化的机制之一。 OBJECTIVE: To investigate the effect of high-fat diet on DNA methylation in atherosclerosis model of Apo E - / - mice by DNA methylation microarray. Methods: Thirty male Apo E - / - mice were randomly divided into normal group and hyperlipidemic group, with 15 rats in each group. The normal group was fed with normal diet and the high fat group was fed with high fat diet. After 16 weeks, blood lipid, serum homocysteine ​​(Hcy) level, serum DNA methylation and serum DNMTs levels were measured. DNA methylation was used to detect the levels of serum Arterial tissue whole genome methylation. Results: Compared with the normal group, serum CHOL, TG and LDL-C in high-fat diet group were significantly increased and HDL-C was significantly decreased; serum DNA methylation level and serum DNA methylation transferase (DNMTs) levels Significantly increased. The result of methylation showed that methylation of 875 genes in the whole aorta of high-fat group changed significantly compared with normal group (P <0.05), and the number of hypermethylated genes was 496 The total number of 56.69%; hypomethylation gene number 379, accounting for 43.31% of the total. Conclusion: High-fat diet can increase the methylation level of aorta genome and decrease the expression of the genome, which may be one of the mechanisms of atherosclerosis in Apo E - / - mice.