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