Effect Of Estrogen On Wnt Signal Pathway In Ovariectomized Rats With Middle Cerebral Artery Occlusion(MCAO)

Objective:To investigate the effects of oestradiol on the Wnt signaling pathway in the middle cerebral artery occlusion(MCAO)model of ovariectomized female Wistar rats,so as to explore the protective effect of estrogen on the central nervous system.Method:Sixty female Wistar rats aged three months were randomly and equally divided as follows:sham operation group(without ovariectomy),model group(ovariectomy),estrogen-treated group[ovariectomy and estrogen replacement,17?p-estrogen,s.c.300 ?g/(kg d)].All rats were developed the model of MCAO with the previous protocol.The brain infarction area was measured with the TTC staining.The expressions of Dkk-1,APC,?-catenin and Survivin were evaluated by immunohistochemistry and western blot.Result:After 24h of MCAO,the mortality of three groups was 0,40%(8/20)and 20%(4/20)respectively.There was no significant difference of mortality between the model group and estrogen-treated group(?~2=1.905,P=0.168).The estrogen-treated group had significantly less infarct volume than the model group[(255.43±51.43)mm~3 versus(490.75±93.38)mm3,t=5.565,P=0.001].The level of E2 of three groups was(31.36±1.89)pg/mL,(18.23±1.08)pg/mL,(35.07±1.46)pg/mL respectively and the difference was significant(F=253.615,P=0.000).Immunohistochemical analysis showed that model group had an increased expression of Dkk-1 and APC compared with sham operation group and estrogen-treated group(P<0.05).The protein expression of ?-catenin 24h after MCAO in the cerebral cortex of estrogen-treated group was significantly increased compared with model group(P<0.05),and there was no significant difference compared with sham operation group(P>0.05).The expression of Survivin was higher in estrogen-treated group compared with model group(P<0.05).Western blotting analysis showed that the expression of Dkk-1 and APC was decreased in cortex of the estrogen-treated group,and that the expression of ?-catenin and Survivin was increased,when compared with the model group(P<0.05).Conclusion:Exogenous oestradiol decreased the APC level,and activate the Wnt/?-catenin signaling pathway,in the cortex of MCAO brain damage in those ovariectomized female rats,suggesting that the hormone replacement therapy plays a protective effect in the central nervous system of brain blood supply insufficiency.