选择性雌激素受体β激动剂对子宫腺肌病模型小鼠孕激素受体和胰岛素样生长因子-1的影响

Effect of Selective Estrogen Receptor β Agonist on Progesterone Receptor and Insulin-like Growth factor-1 in a Mouse Model of Adenomyosis

目的:探讨选择性雌激素β受体(Estrogen Receptor beta,ERβ)激动剂对子宫腺肌病模型小鼠孕激素受体和胰岛素样生长因子-1的影响。方法:子宫腺肌病小鼠(n=30)随机平分为三组-模型组、孕三烯酮组与选择性ERβ激动剂组。模型组每日灌胃蒸馏水0.4 m L/20 g体重,孕三烯酮组每日灌胃孕三烯酮水溶液0.008 mg/20 g体重,选择性ERβ激动剂组每日灌胃WAY-32255水溶液0.008 mg/20 g体重,连续口服14 d。结果:孕三烯酮组与选择性ERβ激动剂组治疗第7 d与第14 d的小鼠体重高于模型组(P<0.05),选择性ERβ激动剂组高于孕三烯酮组(P<0.05)。孕三烯酮组与选择性ERβ激动剂组治疗第7 d与第14 d的子宫病理评分低于模型组(P<0.05),选择性ERβ激动剂组低于孕三烯酮组(P<0.05)。孕三烯酮组与选择性ERβ激动剂组治疗第7 d与第14 d的血清孕激素受体(Progesterone receptor,PR)和胰岛素样生长因子(insulin like growth factor,IGF-1)含量低于模型组(P<005),选择性ERβ激动剂组低于孕三烯酮组(P<0.05)。孕三烯酮组与选择性ERβ激动剂组治疗第7 d与第14 d的子宫RhoA和ROCK蛋白相对表达水平低于模型组(P<0.05),选择性ERβ激动剂组低于孕三烯酮组(P<0.05)。结论:选择性ERβ激动剂对子宫腺肌病模型小鼠的应用能抑制血清PR和IGF-1的释放,降低RhoA和ROCK蛋白的表达,从而能改善子宫病理状况,提高小鼠体重。

Objective:To investigate the effects of selective estrogen receptor beta(ERβ)agonists on progesterone receptor and insulin-like growth factor-1 in a mouse model of adenomyosis.Methods:Adenomyosis mice(n=30)were equally randomly divided into three groups-model group,gestrinone group and selective ERβ agonist group.In the model group,0.4 mL/20 g body weight were given daily with distilled water,the gestrinone group were given 0.008 mg/20 g body weight with gestrinone aqueous solution every day,and the selective ERβ agonist group were given WAY-32255 aqueous solution at 0.008 mg/day 20 g body weight,continuous oral administration for 14 days.Results:The weight of mice in the gestrinone group and the selective ERβ agonist group were higher than that of the model group on the 7th and 14th day(P<0.05),and the selective ERβ agonist group were higher than that of the gestrinone group(P<0.05).The uterine pathological scores of the gestrinone group and the selective ERβ agonist group were lower than the model group on the 7th and 14th day of treatment(P<0.05),and the selective ERβ agonist group were lower than the gestrinone group(P<0.05).The levels of serum progesterone receptor(PR)and insulin like growth factor(IGF)-1 in the gestrinone group and the selective ERβ agonist group on the 7th and 14th day of treatment were lower than those of the model group(P<0.05),the selective ERβ agonist group were lower than the gestrinone group(P<0.05).The relative expression levels of RhoA and ROCK protein in the uterus on the 7th and 14th day of treatment in the gestrinone group and the selective ERβ agonist group were lower than the model group(P<0.05),and the selective ERβ agonist group were lower than the gestrinone group(P<0.05).Conclusion:The application of selective ERβ agonists to adenomyosis model mice can inhibit the release of serum PR and IGF-1,reduce the expression of RhoA and ROCK proteins,thereby improving the pathological conditions of the uterus and increasing the weight of the mice.