A Study About The Intervention Effects Of Phytoestrogens On 17?-Estradiol-Induced Endometrial Exudate And The Vascular Permeability In Ovariectomy Rat

ObjectiveUsing an animal model of vascular hyperpermeability induced by exogenous 17?-estradiol in ovariectomized rat to observe the intervention effects of phytoestrogen Resveratrol(Res),Puerarin(Pue),Biochanin A(Bio)on endometrial exudation and retinal Evans blue(Evans blue,EB),and compare the intervention effects with that of an estrogen receptor modulator tamoxifen(Tam)or an inhibitor of VEGF tyrosinekinase,Sunitinib(Sut);In addition,using enzyme-linked immunosorbent assays(ELISA)to detect the level of serum vascular endothelial growth factor(VEGF)in order to elucidate the related mechanisms.MethodsSixty SD rats were randomly divided into 10 groups,each group had 6 rats:Sham,Ovariectomized(Ovx),Ovx+17?-estradiol(Ovx+Est)(0.1mg·kg-1),Ovx+Est(1.0mg·kg-1),Ovx+Est(0.1mg·kg-1)+Tam,Ovx+Est(1.0mg·kg-1)+Tam,Ovx+Est(O.lmg·kg-1)+Res,Ovx+Est(1.0mg·kg-1)+Pue,Ovx+Est(1.0mg·kg-1)+Bio,Ovx+Est(1.0mg·kg-1)+Sut.After administration of different estrogens for 21 days,we did the following detections:1.calculated the coefficient of the uterus;2.observed endometrial morphological changes 3.counted the eosinophilic granulocyte;4.determinated the retinal vascular permeability using Evans blue;5.determined the concentration of serum VEGF.Results1.Effects of resveratrol on endometrial exudation induced by 17?-estradiol and the concentration of serum VEGF and the level of retina EB of ovariectomy rats.After the ovary removal,we found the rat uterus was atrophic,the body weight,the uterine coefficient and the concentration of serum VEGF decreased,and the exudation of eosinophils in endometrium reduced as well.After administration of exogenous 17?-estradiol(0.1mg·kg-1),the body weight and the uterine coefficient increased,and endometrial hyperplasia appeared,the exudation of eosinophils and the concentration of serum VEGF increased.To compare with Ovx+Est(0.1mg·kg-1)group,the body weight and the uterine coefficient reduced in Ovx+Est(0.1mg·kg-1)+Res group(P<0.05),and the level of retinal EB reduced as well(P<0.05),but the concentration of serum VEGF did not change significantly(P>0.05).2.Effects of Puerarin,Biochanin A and Tamoxifen on endometrial exudation induced by 17?-estradiol and the concentration of serum VEGF and the level of retina EB of ovariectomy rats.To compare Ovx+Est(1.0mg·kg-1)+Pue,Ovx+Est(1.0mg·kg-1)+Bio with Ovx+Est(1.0 mg·kg-1)group respectively,in both of Ovx+Est(1.0mg·kg-1)+Pue and Ovx+Est(1.0mg·kg-1)+Bio groups,the body weight and the uterine coefficient decreased(P<0.05),the endometrium was thinner,moderate amount of eosinophils exudation in endometrial was found,the concentration of serum VEGF decreased.To compare Ovx+Est(1.0 mg-kg-1)+Tam with Ovx+Est(1.0mg·kg-1)group,both the body weight and the uterine coefficient were decreased,only a very small amount of eosinophil cells exudation in the endometrium was found and the concentration of serum VEGF and retinal EB werealso decreased.3.Effects of Sunitinib on endometrial exudation induced by 176-estradiol and the concentration of serum VEGF and the level of retina EB of ovariectomy rats.To compare Ovx+Est(1.0mg·kg-1)+Sut with Ovx+Est(1.0mg·kg-1)group,the body weight and the uterine coefficient decreased,endometrium was thinner,cytoplasm was looser,the exudation of eosinophils in endometrium reduced,the concentration of serum VEGF and retinal EB obvious decreased in Ovx+Est(1.0 mg·kg-1)+Sut group(P<0.01).Conclusions1.Resveratrol,Puerarin,Biochanin A can inhibit the endometrial hyperplasia and exudation that induced by exogenous 176-estradiol,they probably play a role of estrogenic antagonists.2.Puerarin,Biochanin A can reduce the concentration of serum VEGF and the level of retina EB.3.There are inhibitory effects of Tamoxifen on endometrial exudation and the concentration of serum VEGF and the level of retina EB of ovariectomy rats that induced by different dose of 17?-estradiol.4.Puerarin and Biochanin A possess similar effects with Sunitinib and Tamoxifen,suggesting that the effects of these phytoestrogens may related to their blockage of estrogenic receptors and the inhibition of VEGF expression.