米非司酮对小鼠着床期子宫内膜活化的β-连环蛋白(active β-catenin)表达的影响

Effect of Mifepristone on the Expression of Active β-Catenin in Endometrium during the Peri-implantation Period in Mouse

目的:探讨活化的β-连环蛋白(active β-catenin)在胚胎着床过程中的作用。方法:将孕第2日(d2)昆明小鼠随机分成3组,每组30只,A组:孕d2单次背部皮下注射0.1ml米非司酮(1.2mg/ml);B组(溶剂对照):以等量1,3-丙二醇代替米非司酮;C组:不作任何处理。用免疫组织化学、间接免疫荧光、Western blotting方法定性、定量、定位检测3组小鼠在妊娠d3￣7活化的β-连环蛋白的动态表达。结果:B、C组小鼠子宫内膜中活化的β-连环蛋白于孕d3在腺上皮和腔上皮、基质细胞质和细胞膜表达;妊娠d4在腔上皮细胞质和细胞膜强表达,并达高峰;妊娠d5￣7在腺上皮、血管内皮、腔上皮下基质细胞膜和细胞质表达,且B、C组间在妊娠d3￣7各时间点的表达无显著性差异(P>0.05);A组小鼠妊娠d3￣7活化的β-连环蛋白的表达较B、C组显著降低(P<0.01),在妊娠d4表达量未见高峰,且表达部位局限于基质细胞,腔上皮无表达。结论:米非司酮可能通过抑制孕激素与其受体结合而下调活化的β-连环蛋白表达,进而抑制子宫内膜黏附性,影响子宫内膜容受性的建立而阻碍胚胎顺利着床。

Objective：To explore the effect of mifepristone in the embryo implantation of pregnant mice.Methods：Kunming mice on pregnant day 2 were randomly divided into 3 groups with 30 in each group：mifepristone group（group A）was administered with 0.1 ml mifepristone（1.2 mg/ml）by hyodermic on backside;propylene glycol control group（group B）was administered 1,3 propylene glyccol instead of mifepristone with same dose;blank control group（group C）with no treatment.Expression of active β-catenin protein in endometrium of pregnant mice was detect from day 3 to day 7 of pregnancy by immunohistochemistry,Western blotting and immunofluorescence.Results：The expression of active β-catenin protein was significantly increased and reached its peak on pregnant day 4 in group B and group C,but there was no difference in the expression of active β-catenin between the two groups（P0.05）.The levels of active β-catenin protein in group A were significantly lower than those in groups B and C（P0.01）,and there was no peak expression on pregnant day 4.Conclusion：Mifepristone probably down-regulated the expression of β-catenin through inhibiting progestogen combined with its receptor,furthermore inhibited the adhesion of endometrium and influenced the establishment of endometrial receptivity,so as to obstruct the embryo implantation.