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  

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

作　　者：陈瑛[1] 赵焕英[2] 任新瑜[3] 

机构地区：[1]首都医科大学附属北京友谊医院,100050 [2]首都医科大学医学实验与测试中心 [3]中国医学科学院北京协和医学院北京协和医院病理科

出　　处：《国际生殖健康／计划生育杂志》2015年第3期193-195,共3页Journal of International Reproductive Health/Family Planning

基　　金：国家自然科学基金资助项目(30901598)

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 m L/d(模型组);戊酸雌二醇0.13 m L/d+地屈孕酮0.13 m L/d(HT组);ICI皮下注射0.13 m L/周+戊酸雌二醇0.13 m L/d(ICI+E2组);ICI皮下注射0.13 m L/周+戊酸雌二醇0.13 m L/d+地屈孕酮0.13 m L/d(ICI+HT组);戊酸雌二醇0.13 m L/d+PHTTP 0.13 m L/d(PHTTP+E2组);戊酸雌二醇0.13m L/d+地屈孕酮0.13 m L/d+PHTTP 0.13 m L/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m RNA含量。结果:各组NF-κB m RNA的表达差异有统计学意义(P<0.05),而MMP-9 m RNA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。Objective： To observe the effects of estrogen and its receptor modulators on the expressions of NF-KB 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 PHTYP＋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 PHTT＋E2 group and the PHTFP＋HT group had significantly higher expressions of NF- κB mRNAs （P=0.047 和 P=0.035）. The NF-KB expression in the ICI＋HT group was significantly lower than that in the PHTFP＋HT group （P=0.028）. However, there were not significantly differences in NF-KB 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 ERa （PHTrP＋E2 and PHTrP＋HT） increases the expression of NF-KB in atherosclerotic tissues,which indicated that ERa might increase the instability of atherosclerotic.

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 

分 类 号：R965[医药卫生—药理学]