Hhcy诱导基因组低甲基化作用的研究

目的 探讨高同型半胱氨酸血症（Hhcy）对大鼠主动脉组织基因组总甲基化水平的影响.方法 健康6周龄雄性Wistar大鼠24只,体重（160±10）g,适应性喂养1周后分为对照组与高同型半胱氨酸组,每组12只.对照组饲以AIN-93G配方饲料,高同型半胱氨酸组予以含1.7%甲硫氨酸的AIN-93G配方饲料.喂养18周后,全自动生化仪测定血浆（同型半胱氨酸）Hcy浓度,电镜观察主动脉组织形态学变化,改进酶联免疫吸附测定法（ELISA）检测主动脉组织DNA甲基转移酶活力和基因组总甲基化水平.结果 18周蛋氨酸饮食可诱导Hhcy,电镜染色主动脉组织呈现动脉粥样硬化早期形态学变化,高同型半胱氨酸组主动脉组织DNA甲基转移酶活力和基因组总甲基化水平明显低于对照组（P＜0.05）.结论 Hhcy诱导基因组低甲基化可能是其参与动脉粥样硬化的机制之一.

Effect of hyperhomocystinemia induced by ingestion of excess methionine on global DNA methylation in rats

Objective To investigate the effects of hyperhomocystinemia induced by ingestion of excess methionine on global DNA methylation status in aorta of rats. Methods 24 healthy Wistar rats were randomly divided into control group （ n = 12）, hyperho mocysteinemia group （n = 12）. The control group was fed with AIN -93G diet. The hyperhomocysteinemia group was fed with high - methionine diet, consisting of AIN -93G diet plus 1.7% methionine. After 18 weeks, the homocysteine concentration in the plasma was measured. The thoracic aorta was harvested for morphology （ electron microscopy）. The DNA methyhransferase activity and global DNA methylation was determined using an innovative enzyme - linked immunosorbent assay （ELISA）. Results A high methionine diet for 18 weeks was sufficient to induce hyperhomocystinemia and early atherosclerosis morphological change by electron microscopy;compared with the control group, the Hhcy group had a decreased DNA methyltransferase activity and global DNA methylation status （P 〈 0.05 ）. Conclusion Global DNA hypomethylation may play an important role in the pathogenesis of Hhcy induced atherosclerosis.