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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。
Objective To investigate the effect of hyperhomocysteinemia (Hcy) on the total genomic DNA methylation in rat aorta. Methods Twenty-four male Wistar rats, 6 weeks old, weighing 160 ± 10 g, were randomly divided into control group and hyperhomocysteine group, 12 rats in each group. The control group was fed the AIN-93G formula diet, and the high homocysteine group was given the AIN-93G formula diet containing 1.7% methionine. After 18 weeks of feeding, Hcy concentration in plasma (homocysteine) was measured by automatic biochemical analyzer. Morphology changes of aorta were observed by electron microscope. DNA methyltransferase activity of aorta tissue was detected by enzyme linked immunosorbent assay (ELISA) And total genomic methylation levels. Results Methionine diet induced Hhcy at 18 weeks. The morphological changes of the aorta were observed at the early stage of atherosclerosis by electron microscopy. The levels of DNA methyltransferase and genomic methylation in the aorta of the homocysteine group were significantly lower than those of the Hcy Control group (P <0.05). Conclusion Hhcy-induced genomic hypomethylation may be one of the mechanisms involved in atherosclerosis.