米非司酮对子宫肌瘤大鼠性激素、Wnt/β-catenin通路的影响  

Effect of Mifepristone on Sex Hormone and Wnt/β-catenin Pathway in Uterine Fibroids Rats

作　　者：张瑞[1] 聂敦利[1] 陈妍[1] 曾韵兰[1] ZHANG Rui;NIE Dunli;CHEN Yan;ZENG Yunlan(Department of Obstetrics and Gynecology,Chengdu First People's Hospital,Chengdu 610016,China)

机构地区：[1]成都市第一人民医院妇产科,成都610016

出　　处：《宁夏医科大学学报》2020年第9期885-890,共6页Journal of Ningxia Medical University

摘　　要：目的探讨米非司酮作用子宫肌瘤大鼠的疗效及作用机制。方法采用雌激素加孕激素负荷法建立子宫肌瘤大鼠模型,对造模成功大鼠20只随机分为模型组和米非司酮组,另取10只正常大鼠作为空白组。空白组、模型组腹腔内注射2 mL 0.9%氯化钠溶液,米非司酮组腹腔内注射2.24 mg·kg^-1米非司酮溶液,每天1次,共28 d。末次给药24 h后,大鼠称重并处死,子宫称重,计算子宫系数;通过HE染色观察子宫组织病理变化;ELISA检测血清雌二醇(E2)、孕激素(P)、黄体生成素(LH)水平;免疫组化检测子宫组织雌激素受体(ER)、孕激素受体(PR)、血清表皮生长因子(EGF)及表皮生长因子受体(EGFR)表达;Western blot检测子宫组织Wnt5b、β-catenin水平。结果模型组较空白组子宫组织病理明显变化,E2、P、LH、ER、PR、EGF、EGFR、Wnt5b、β-catenin水平及子宫系数均升高(P均<0.05);米非司酮组较模型组子宫组织病理变化明显改善,E2、P、LH、ER、PR、EGF、EGFR、Wnt5b、β-catenin水平均降低(P均<0.05)。结论米非司酮对大鼠子宫肌瘤有疗效,其抗瘤机制可能与降低体内ER、PR水平,抑制EGF、EGFR对肿瘤的增殖刺激作用,抑制Wnt5b、β-catenin的表达有关。Objective To investigate the efficacy and mechanism of mifepristone in rats with uterine fibroids.Methods Establishing rat model of uterine fibroids by estrogen plus progestin loading method,and rats with successful modeling were randomly divided into a model group and a mifepristone group,and another 10 normal rats were used as a control group.The control group and the model group were intraperitoneally injected with 2 m L of 0.9%sodium chloride solution,and the mifepristone group was intraperitoneally injected with 2.24 mg·(kg·d)^-1 mifepristone solution,continuous administration for 28 days.After 24 hours of the last administration,the rats were weighed and sacrificed,and the uterus was weighed to calculate the uterine coefficient,the pathological changes of uterus were observed by HE staining.The levels of E2,P and LH in serum were detected by ELISA.The expressions of ER,PR,EGF and EGFR in uterus were detected by Immunohistochemistry.The levels of Wnt5 b and β-catenin in uterus were detected by Western blot.Results The pathological changes of uterus and the levels of E2,P,LH,ER,PR,EGF,EGFR,Wnt5 b,β-catenin and the uterus coefficient were significantly increased in the model group compared with the control group(P all<0.05).The mifepristone group compared with the model group were significantly improved the pathological changes of uterus and significantly decreased the levels of E2,P,LH,ER,PR,EGF,EGFR,Wnt5 b andβ-catenin(P all<0.05).Conclusion Mifepristone has obvious curative effect on rat uterine fibroids,and its anti-tumor mechanism may be related to reducing ER and PR levels,inhibiting the proliferation of EGF and EGFR on tumors,and inhibiting the expression of Wnt5 b andβ-catenin.

关 键 词：子宫肌瘤 米非司酮 表皮生长因子 雌激素受体 孕激素受体 

分 类 号：R737.33[医药卫生—肿瘤] R984[医药卫生—临床医学]