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