Study On The Space-time Of Estrogen Effect Related Correlators In Adenomyosis Mice Model By Therapy Of Expelling Dampness And Dissipating Blood Stasis

Objective By dampness-resolving and stasis-dissolving method,to observe the effects of estrogen-responsive factors p-STAT3,17β-HSDI,and 17β-HSDII in AM mice during different estrus cycles,in the endometrium and ectopic endometrium expression.Exploring the mechanism of dampness-resolving and stasis-dissolving method affecting the development of AM by interfering with estrogen effects.Providing scientific evidence for clinical popularization and application to AM therapy of dampness-resolving and stasis-dissolving method.Methods The same male rat pituitary suspension was injected into the right uterine cavity of 8-week-old ICR female mice to establish AM model.After the completion of modeling,they are randomly divided into the following 7 groups:3 months model group（3M）,6 months model group（6M）,low,medium and high dose of Neiyikangfupian（NYKFP）group,Danefukangjiangao group（DEFKJG）and Gestrinone group（GES）.Also is equipped with sham operationgroup（Sham）and normal group（Normal）.Each group had 24 mice.Fed the mice of Normal group,sham-operation group and 3 months group 3 months,then killed them in oestrus period and anoestrus period respectively.The mice of the rest group were killed in oestrus and anoestrus after 3 months gavage.Observed the pathological changes of mice endometrium and graded AM severity by hematoxylin-eosin stain.Tested p-STAT3,17β-HSDI,17β-HSDII expression of mice uterine tissues respectively with immunohistochemistry.Results1.The results of the mechanisms of AM:Compared the degree of AM severity with Normal group,there was no significant difference in the Sham group（P>0.05）,3months group and 6 months group increased significantly（P<0.05）;6 months group is higher than 3 months group（P<0.01）.Compared the expression of p-STAT3 and17β-HSDI with Normal group,there was no significant difference in the Sham group（P>0.05）,3 months group and 6 months group increased significantly（P<0.01）;6 months group is higher than 3 months group（P<0.01）.Compared the expression of17β-HSD II with Normal group,there was no significant difference in the Sham group（P>0.05）,3 months group and 6 months group decreased significantly（P<0.01）;6 months group is lower than 3 months group（P<0.01）.2.The result of the efficacy and function mechanisms of NYKFP:Compared the degree of AM severity with 6 months group,low dose of NYKFP group has no statistically significant difference（P>0.05）,the rest of groups decreased significantly（P<0.05）.The expression of p-STAT3 and 17β-HSDI,compared with 6 months group,medium dose of NYKFP group,high dose of NYKFP group,DEFKJG group and GES group decreased significantly（P<0.01）;compared with high dose of NYKFP group,the DEFKJG group and the GES group were higher（P<0.01）;NYKFP low,middle and high dose groups were statistically significant difference（P<0.01）.The expression of 17β-HSD II,compared with 6 months group,medium dose of NYKFP group,high dose of NYKFP group,DEFKJG group and GES group increased significantly（P<0.05）;compared with high dose of NYKFP group,the DEFKJG group and the GES group were lower（P<0.01）;NYKFP low,middle and high dose groups were statistically significant difference（P<0.01）.3.The expression of p-STAT3 and 17β-HSDI in GES group eutopic endometrium,which are no statistically significant difference compared oestrus with anoestrus（P>0.05）.In the rest of model groups,the expression of p-STAT3 and17β-HSDI in oestrus is higher than anoestrus（P<0.05）,the expression of 17β-HSDII in anoestrus is higher than oestrus（P<0.01）.The expression of p-STAT3 and17β-HSDI,ectopic endometrium is higher than eutopic endometrium in each model group（P<0.01）.The expression of 17β-HSDII,ectopic endometrium is lower than eutopic endometrium in each model group（P<0.01）.4.There was a positive correlation between AM grading score and the expression of p-STAT3,17β-HSD I;and a negative correlation between AM grading score and expression of 17β-HSD II in both oestrus and anoestrus（P<0.05）.There was a positive correlation between expression of p-STAT3 and 17β-HSD I,and a negative correlation between expression of p-STAT3 and 17β-HSD II,17β-HSD I and17β-HSD II（P<0.01）.Conclusions1.The occurrence of AM is related to the high expression of p-STAT3 and17β-HSDI,the low expression of 17β-HSDII.2.The dampness-resolving and stasis-dissolving method can by decrease the expression of p-STAT3 and 17β-HSDI,increase the expression of 17β-HSDII in ectopic endometrium and eutopic endometrium,to decrease the production of E₂,affect occurrence and development of AM.At the same time,can decrease the activation of p-STAT3,to decrease invasive of eutopic endometrium,achieveing the goal of treatment for AM.3.The effect of NYKFP to p-STAT3,17β-HSDI,17β-HSDII have dose relativity,high dose>medium dose>low dose.The effect of high dose of NYKFP is better than DEFKJG group and GES group.4.The expression of p-STAT3,17β-HSDI,17β-HSDII change with the change of estrus cycle.The estrogen effect in oestrus is higher than anoestrus,which can be accorded to elect the best time of taking medicine for AM.