基础医学与临床 ›› 2010, Vol. 30 ›› Issue (1): 63-66.

• 研究论文 • 上一篇    下一篇

多囊卵巢综合征大鼠模型LHR、INSR、AR基因甲基化的变化

朱亮 邢福祺 全松 张文颖 杜建新   

  1. 解放军第306医院 南方医院妇产科生殖医学中心 南方医院妇产科生殖医学中心 解放军第306医院
  • 收稿日期:2008-05-28 修回日期:2009-06-15 出版日期:2010-01-05 发布日期:2010-01-05
  • 通讯作者: 朱亮

Changes of LHR, INSR, AR genes' methylation in rat polycystic ovarian syndrome model

Liang ZHU, Fu-qi XING, Song QUAN, Wen-ying ZHANG, Jian-xin DU   

  1. the 306 Hospital of PLA Assisted Reproductive Center, Nan-Fang Hospital
  • Received:2008-05-28 Revised:2009-06-15 Online:2010-01-05 Published:2010-01-05
  • Contact: Liang ZHU,

摘要: 目的 复制一种理想的多囊卵巢综合征(PCOS)动物模型,并检测LHR、INSR和AR基因DNA甲基化状态。方法 给模型组24日龄大鼠皮下埋植左旋18-甲基炔诺酮硅胶棒3mm/只,3d后每日2次皮下注射人绒毛膜促性腺激素1.5 IU。给对照组皮下注射等体积生理盐水。注射9d后观察大鼠卵巢形态学(HE染色)、放射免疫法测定性激素和空腹胰岛素水平、己糖激酶法测定空腹血糖水平、计算胰岛素抵抗(HOMA)指数。用甲基化特异性PCR检测LHR、INSR和AR基因的DNA甲基化状态。结果 模型组大鼠卵巢重量和体积均显著高于对照组(P<0.001)。模型组卵巢各级发育期卵泡及黄体少见,卵泡多呈囊性扩张。模型组大鼠血清孕激素、睾酮、促黄体生成激素(LH)、空腹胰岛素、空腹血糖水平均显著高于对照组(P均<0.05);LH/促卵泡生长激素(FSH)比值和HOMA指数也均显著高于对照组(P均<0.001)。模型组INSR基因甲基化率为76.7%,显著高于对照组(20.0%)(P<0.001)。结论 DNA甲基化介导的胰岛素受体基因转录抑制是PCOS胰岛素抵抗发生机制之一。

关键词: 多囊卵巢综合症, DNA甲基化, 动物模型

Abstract: Objective To establish an ideal model animal of PCOS and to detect the DNA methylation states of LHR, INSR and AR genes in this model. Methods 24-days-old female Sprague-Dawley (SD) rats were randomly divided into two groups. The rats in the experimental group were given subcutaneous implanting of levonorgestrel silica gel staff (3mm per rat) and begun to inject 1.5 IU hCG twice daily for 9 days from the 4th day. The rats in the control group were injected with normal saline at the same time. Ovarian morphologic changes, sex hormone levels, fasting serum insulin and glucose were detected. The LHR, INSR and AR genes' DNA methylation patterns were checked by methylation specific PCR in modeling group and control group. Results The ovarian weight and volume in modeling group were higher than those in control group (both P< 0.001). The ovaries in modeling group showed multiple follicular cysts, and the number of theca cells and interstitial cells increased. Less developing follicles and corpus lutea were seem. The serum level of progesterone, testosterone, luteinizing hormone, fasting insulin and glucose were significantly higher in experimental group than those in control group (P<0.05), so as the LH/FSH ratio and HOMA index (both P< 0.001). No methylation of LHR and AR genes were detected in both groups. The methylation frequency of INSR gene (76.7%) was significantly higher in modeling group than that in control group (P< 0.001). Conclusions The depression of INSR gene's transcriptional induced by DNA methylation is a good supplement to he pathogenesis of insulin resistance in PCOS.

Key words: PCOS, DNA methylation, animal model