同型半胱氨酸经甲基化修饰下调去卵巢大鼠主动脉雌激素受体α基因的表达

基础医学与临床 ›› 2008, Vol. 28 ›› Issue (3): 243-246.

同型半胱氨酸经甲基化修饰下调去卵巢大鼠主动脉雌激素受体α基因的表达

刘军须张敬各

河北医科大学河北医科大学

收稿日期:2007-04-23 修回日期:2007-07-31 出版日期:2008-03-25 发布日期:2008-03-25
通讯作者: 刘军须

Homocysteine downregulates the estrogen receptor alpha expression in aorta of ovariectomized rats by methylation modification

Jun-xu LIU Jing-ge ZHANG

Department of Laboratory Animal Science,Hebei Medical University

Received:2007-04-23 Revised:2007-07-31 Online:2008-03-25 Published:2008-03-25
Contact: Jun-xu LIU

摘要/Abstract

摘要： 目的观察同型半胱氨酸(Hcy)对大鼠雌激素受体α (ERα) 基因表达和其启动子CpG岛甲基化的影响。方法高效液相色谱仪检测血浆Hcy水平；RT-PCR和甲基化特异性PCR(MSP) 分别检测ERα mRNA表达水平及基因启动子CpG岛的甲基化状态。结果去卵巢和给予甲硫氨酸饮食均可升高大鼠血浆Hcy水平。去卵巢和Hcy均可使大鼠ERα mRNA表达减少，但5'-Aza 可使细胞ERα mRNA表达增多。假手术组大鼠主动脉ERα基因启动子有2例 (20%) 存在甲基化，去卵巢组有3例 (30%) 存在甲基化，而去卵巢＋Hcy组有6例 (60%) 存在甲基化；对照组细胞ERα启动子CpG岛完全去甲基化，Hcy组细胞甲基化增强，5'-Aza使细胞去甲基化。结论 Hcy可经甲基化修饰方式下调去卵巢大鼠主动脉ERα mRNA表达。

关键词: 同型半胱氨酸, 雌激素受体, 甲基化, 大鼠

Abstract: Objective To observe the effects of homocysteine on the expression of estrogen receptor alpha (ERα) mRNA and the CpG island methylation of ERα gene promotor region in rats. Methods The serum levels of homocysteine in rats were measured by reversed- phase high performance liquid chromatography. RT-PCR and methylated specific PCR (MSP) assayed the mRNA expression and the methylation status in promoter CpG island of ERα gene in aorta and cultured rat aortic smooth muscle cells (RASMCs) respectively. Results The homocysteine levels were increased in ove and ove＋H groups (P<0.05 or P<0.01). The mRNA expression of ERα decreased in both ove and Hcy groups，while increased in cells treated with 5'-Aza. The methylation of CpG island in promoter region of ERα gene in aorta increased approaching 30% in ove group and 60% in ove+H group compared with 20% in sham group. The CpG island in ERα gene promotor region was completely demethylated in control RASMCs, and Hcy induced hypermethylation, while 5'-Aza produced demethylation. Conclusion Homocysteine downreglates the estrogen receptor alpha expression in aorta of ovariectomized rats by methylation modification manner.

Key words: homocysteine, estrogen receptor, methyaltion, rats

刘军须张敬各. 同型半胱氨酸经甲基化修饰下调去卵巢大鼠主动脉雌激素受体α基因的表达[J]. 基础医学与临床, 2008, 28(3): 243-246.

Jun-xu LIU Jing-ge ZHANG. Homocysteine downregulates the estrogen receptor alpha expression in aorta of ovariectomized rats by methylation modification[J]. Basic & Clinical Medicine, 2008, 28(3): 243-246.

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