GnRHa对改善他莫西芬诱发子宫腺肌病小鼠模型内膜容受性的作用

Effect of GnRH Agonist on Endometrial Receptivity in Tamoxifen Induced Uterine Adenomyosis in Mice

目的：探讨促性腺激素释放激素激动剂（GnRHa）对腺肌病模型小鼠种植窗期内膜容受性的影响。方法：新生ICR小鼠滴喂他莫西芬建立子宫腺肌病模型,随机分为GnRHa降调的模型鼠组（A组）、模型对照鼠组（B组）,并取同龄正常小鼠作为对照组（C组）,每组8只,于100~115日龄处死,HE染色检测小鼠子宫病理变化;免疫组织化学CD31染色计算小鼠子宫微血管密度;免疫组织化学法检测种植窗期子宫内膜LIF表达及扫描电镜下观察胞饮突发育情况。结果：①口服他莫西芬法建立ICR小鼠子宫腺肌病模型造模率为100%,B组小鼠子宫肌层微血管密度高于A、C组,差异有统计学意义（P〈0.05）。②种植窗期子宫内膜LIF蛋白水平A组和C组明显高于B组,差异有统计学意义（P〈0.05）;A、C组间无统计学差异（P〉0.05）。③B组可见较多退化的胞饮突,分布稀疏,呈局灶性分布;A组的胞饮突较B组丰富但大小略不均;C组胞饮突分布较丰富且发育完全。结论：新生小鼠口服他莫西芬法可高效建立子宫腺肌病模型,GnRHa降调节能改善子宫腺肌病小鼠子宫内膜中LIF表达及胞饮突发育,从而提高子宫内膜容受性。

Objective： To investigate the effect of GnRHa prolonged down-regulation on endometrial expression of leukaemia inhibitory factor（LIF） and pinopodes in＂implantation window＂of adenomyosis model mice.Methods： ICR mice with adenomyosis were induced by orally administration of tamoxifen on days 2-5 after birth.Drug and control mice were divided into three groups： group A（adenomyosis model with GnRHa）,group B（adenomyosis model with saline）,group C（control with saline）.Hematoxylin and eosin（HE） staining was performed to examine the histopathological changes of all mice.Microvessel density（MVD） was assessed by immunohistochemistrial staining with CD31.LIF protein was determined by immunohistochemistry,and pinopodes were investigated by scanning electronic microscopy（SEM） in the uterine endometrium in＂implantation window＂of mice.Results： 1） The success rate of mouse adenomyosis model established by oral tamoxifen administration reached 100%.The MVD of mouse uterine myometrium in group B was higher than that in group A or group C（P0.05）.2） In＂implantation window＂of mice,LIF level in group A or group C was significantly higher than that in group B（P0.05）.There were no significant difference of LIF level between group B and C.3） The regressing pinopodes were observed in group B,and developed much less than group C（P0.05）.In groups A and C,there were large fully developed pinopodes in endometrial surface.But the size of pinopodes distribution in group A was not equal.Conclusion： It＇s an efficient way to establish the mouse model of adenomyosis induced by oral tamoxifen adiministration.Mouse model of adenomyosis with GnRHa administration increase the expression of endometrial LIF and improved the development of pinopodes,and so GnRHa administration may improve uterine receptivity.