国际生殖健康/计划生育杂志

国际生殖健康/计划生育 ›› 2015, Vol. 34 ›› Issue (3): 193-195.

• 论著 • 上一篇    下一篇

雌激素及其受体调节剂对去势APOE基因敲除小鼠胸主动脉中NF-κB和MMP-9的影响

陈瑛，赵焕英，任新瑜
   

  1. 100050 首都医科大学附属北京友谊医院（陈瑛）； 首都医科大学医学实验与测试中心（赵焕英）；中国医学科学院 北京协和医学院 北京协和医院病理科（任新瑜）
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2015-05-15 发布日期:2015-05-15
  • 通讯作者: 陈瑛

Effects of Estrogen and its Receptor Modulators on NF-κB and MMP-9 Expression in Thoracic Aorta Tissues of Castrated APOE-/- Mice

CHEN Ying，ZHAO Huan-ying，REN Xin-yu   

  1. Beijing Friendship Hospital, Capital Medical University，Beijing 100050，China（CHEN Ying）；Core Facilities center, Capital Medical University, Beijing 100069, China（ZHAO Huan-ying）；Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing 100730, China（REN Xin-yu）
  • Received:1900-01-01 Revised:1900-01-01 Published:2015-05-15 Online:2015-05-15
  • Contact: CHEN Ying

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摘要： 目的：观察雌激素及其受体调节剂对去势APOE基因敲除（APOE-/-）小鼠胸主动脉血管组织中NF-κB和MMP-9的影响。方法：44只APOE-/-小鼠喂养4 周, 确定动脉粥样硬化斑块形成后, 将其随机分成模型组和5组不同给药组：生理盐水0.2 mL/d（模型组）；戊酸雌二醇0.13 mL/d + 地屈孕酮0.13 mL/d（HT组）；ICI 皮下注射0.13 mL/周+戊酸雌二醇0.13 mL/d（ICI+E2组）；ICI 皮下注射0.13 mL/周+戊酸雌二醇0.13 mL/d+地屈孕酮0.13 mL/d（ICI+HT组）；戊酸雌二醇0.13 mL/d+PHTTP 0.13 mL/d（PHTTP+E2组）；戊酸雌二醇0.13 mL/d+地屈孕酮0.13 mL/d+PHTTP 0.13 mL/d（PHTTP+HT组）。8周后，获取动脉粥样硬化斑块的胸主动脉组织后行总RNA提取、逆转录，利用real-time PCR 检测小鼠胸主动脉NF-κB和MMP-9的mRNA含量。结果：各组NF-κB mRNA 的表达差异有统计学意义（P＜0.05），而MMP-9 mRNA 的表达差异无统计学意义（P＞0.05）。与模型组相比，PHTTP+E2和PHTTP+HT组NF-κB表达显著升高（P=0.047和P=0.035），ICI+HT组NF-κB的表达明显低于PHTTP+HT组（P=0.028）；模型组、HT组、ICI+E2组及ICI+HT组间NF-κB的表达差异不明显（与模型组相比，P分别为0.072，0.068和0.054）。结论：ERα介导的激素替代治疗（PHTTP+E2和PHTTP+HT）使NF-κB的表达升高，提示ERα可能对动脉粥样硬化斑块稳定性不利。

关键词: 绝经期, 动脉粥样硬化斑块, 雌激素替代疗法, 雌激素受体α, 雌激素受体β

Abstract: Objective: To observe the effects of estrogen and its receptor modulators on the expressions of NF-κB and MMP-9 mRNAs in the thoracic aorta tissues of the castrated APOE-/- mice. Methods: The model of atherosclerotic plaque was developed by 44 castrated APOE-/- mice. These mice were randomly divided into 6 groups:①the control group: saline 0.2 mL/d;②the HT group：progynova 0.13 mL/d plus dydro-gesterone 0.13 mL/d；③the ICI+E2 group：ICI subcutaneous injection 0.13 mL/week plus progynova 0.13 mL/d；④the ICI+HT group：ICI subcutaneous injection 0.13 mL/week, progynova 0.13 mL/d plus dydro-gesterone 0.13 mL/d; ⑤the PHTTP+E2 group：progynova 0.13 mL/d plus PHTTP 0.13 mL/d；⑥the PHTTP+HT group：progynova 0.13 mL/d plus dydro-gesterone 0.13 mL/d plus PHTTP 0.13 mL/d. After 8 weeks treatment，total RNA were extracted from the atheroselerotic plaque tissues. Expressions of NF- κB and MMP-9 mRNAs were detect using real-time PCR. Results: There was not significant difference in the expression of MMP-9 mRNA among 6 groups（P＞0.05）, while there was significant difference in NF-κB mRNA among 6 groups（P＜0.05）. Compared with the control group, the PHTTP+E2 group and the PHTTP+HT group had significantly higher expressions of NF- κB mRNAs（P=0.047和P=0.035）. The NF-κB expression in the ICI+HT group was significantly lower than that in the PHTTP+HT group（P=0.028）. However, there were not significantly differences in NF-κB expression among the control group, HT group, ICI+E2 group and ICI + HT group（compared with the control group, the values of P were 0.072,0.068 and 0.054, respectively）. Conclusions: The hormone replacement therapy mediated by ERα（PHTTP+E2 and PHTTP+HT） increases the expression of NF-κB in atherosclerotic tissues，which indicated that ERα might increase the instability of atherosclerotic.

Key words: Menopause, Atherosclerotic plaque, Estrogen replacement therapy, Estrogen receptor alpha, Estrogen receptor beta