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高同型半胱氨酸血症和高胆固醇血症联合作用对大鼠基因组DNA总甲基化状态的影响

王义勇1,罗彩琴1,2,丛广志1,2,贾绍斌3   

  1. 1. 宁夏医科大学
    2.
    3. 宁夏医科大学总院心脏中心
  • 收稿日期:2011-09-02 修回日期:2011-11-14 出版日期:2012-02-15 发布日期:2012-02-15
  • 通讯作者: 贾绍斌

Combined Effects of Hyperhomocysteinemia and Hypercholesterolemia on genomic DNA methylation in Wistar rats

  • Received:2011-09-02 Revised:2011-11-14 Published:2012-02-15 Online:2012-02-15

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2009

摘要： 摘要 目目的：探讨高同型半胱氨酸血症（HHCY）和高胆固醇血症(HTC)联合作用对大鼠主动脉基因组DNA总甲基转移酶活力（DNMT）及总甲基化水平的影响。方法：44只健康清洁级成年Wistar雄性大鼠按2×2析因设计随机分为阴性对照组、高同型半胱氨酸（homocysteine, HCY）组、高总胆固醇（total cholesterol, TC）组、高HCY+高TC组，每组11 只。对照组给予普通大鼠饲料，其余各组给予相应的配方饲料。喂养3个月后心脏取血检测血清中HCY、TC等相关指标。提取主动脉基因组DNA检测基因组DNA总甲基化水平;提取主动脉核蛋白检测基因组DNA总甲基转移酶活力。结果：HHCY和HTC联合作用大鼠血清HCY较高，产生相互作用（P<0.01），表现为协同作用，而对大鼠血清TC、TG、LDL-C、HDL-C无交互作用。HHCY和HTC联合作用主动脉基因组DNA总甲基转移酶活力较高，产生相互作用（P<0.01），表现为协同作用，总基因组DNA甲基化水平降低也就是去甲基化程度的增加，产生相互作用（P<0.01），表现为协同作用。结论：HHCY和HTC联合作用使得大鼠主动脉基因组DNA总DNMT活力增高，基因组DNA总甲基化水平降低，可能是AS发生发展的重要机制之一。

关键词: 动脉粥样硬化, 高胆固醇血症, 高同型半胱氨酸血症, DNA甲基转移酶, 基因组DNA甲基化

Abstract: Objective: To study the combined effects of hyperhomocysteinemia and hypercholesterolemia on genomic DNA methylation and DNA methyltransferase activity in aortic tissue of Wistar rats.Methods: 44 healthy clean level male Wistar rats were 2x2 factorial design randomized into four groups: negative control group, high-homocysteine group ， high-cholesterol group，High homocysteine mixed of high cholesterol group. The rats in negative control group were fed a normal chaw, and the other three groups were fed a chaw formula as designed.The rats were fed for three months. Heart blood was then drawn for detection of serum homocysteine and cholesterol; aortic genomic DNA was extracted for detection of genomic DNA methylation levels; and aortic nucleoprotein was extracted for detection of DNA methyltransferase activity.Results: Hyperhomocysteinemia combined effects of hypercholesterolemia increased serum homocysteine level， and there was significant statistics difference (P<0.01) ,make the performance for synergies，but there was no significant difference in rats total cholesterol (TC)、triglyceride (TG)、low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels by hyperhomocysteinemia combined effects of hypercholesterolemia (P>0.05). Hyperhomocysteinemia combined effects of hypercholesterolemia increased aortic genomic DNA methyltransferase activity ,and there was significant statistics difference(P<0.01) ,make the performance for synergies, and promoted aortic genomic DNA demethylation (P<0.01) ,make the performance for synergies effect.Conclusion: Hypomethylation and High-methyltransferase activity induced by hyperhomocysteinemia and the combined effects of hypercholesterolemia is one of the important mechanisms for the development of atherosclerosis.

Key words: atherosclerosis, hypercholesterolemia, hyperhomocysteinemia, DNA methyltransferases, DNA methylation