他莫昔芬联合左炔诺孕酮对大鼠子宫肌瘤的影响及机制研究  

Effects of tamoxifen combined with levonorgestrel on uterine fibroids in rats and their mechanism

作　　者：徐霞 张红[2] 王鹏程 韩璐 XU Xia;ZHANG Hong;WANG Pengcheng;HAN Lu(Department of Gynecology,Suzhou Kowloon Hospital,Shanghai Jiao Tong University School of Medicine,Suzhou 215000,China)

机构地区：[1]上海交通大学医学院苏州九龙医院妇科,江苏苏州215000 [2]苏州大学附属第一人民医院妇科,江苏苏州215006

出　　处：《陕西医学杂志》2024年第5期589-592,597,共5页Shaanxi Medical Journal

基　　金：江苏省青年医学重点人才项目(QNRC2016217)。

摘　　要：目的:探讨他莫昔芬联合左炔诺孕酮对大鼠子宫肌瘤的影响及其作用机制。方法:选择SPF级成年雌性SD大鼠30只,采用苯甲酸雌二醇联合黄体酮腹腔注射建立子宫肌瘤模型。将大鼠随机分为对照组(正常大鼠2 ml 0.9%氯化钠溶液灌胃)、模型组(子宫肌瘤大鼠2 ml 0.9%氯化钠溶液灌胃)、他莫昔芬组(子宫肌瘤大鼠1.70 mg/kg他莫昔芬灌胃)、左炔诺孕酮组(子宫肌瘤大鼠0.1 mg/kg左炔诺孕酮灌胃)和联合组(子宫肌瘤大鼠他莫昔芬联合左炔诺孕酮灌胃),每组6只,连续灌胃30 d。ELISA检测大鼠血清雌二醇(E2)、孕激素、促卵泡激素(FSH)、促黄体生成素(LH)水平。测量子宫系数、左右宫颈角长度及宫角最大直径。HE染色观察子宫组织结构及内膜厚度。Western blot检测子宫组织Wnt5b、β-连环蛋白(β-catenin)蛋白表达。结果:与对照组比较,模型组血清E2、孕激素、FSH、LH水平升高(均P<0.05)。联合组血清E2、孕激素、FSH、LH水平低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。模型组子宫系数、左右宫颈角长度、宫角最大直径及子宫内膜厚度较对照组增加(均P<0.05)。联合组子宫系数、左右宫颈角长度、宫角最大直径及子宫内膜厚度低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。联合组子宫损伤程度较模型组减轻。模型组子宫组织Wnt5b、β-catenin蛋白表达高于对照组(均P<0.05)。联合组Wnt5b、β-catenin蛋白表达低于他莫昔芬组和左炔诺孕酮组(均P<0.05)。结论:他莫昔芬联合左炔诺孕酮能够缩小大鼠子宫肌瘤,改善子宫形态,抑制子宫平滑肌细胞增大,其机制可能与抑制Wnt/β-catenin通路有关。Objective:To investigate the effects of tamoxifen combined with levonorgestrel on uterine fibroids in rats and their mechanism.Methods:Thirty adult female SD rats with SPF grade were selected to establish uterine fibroid model by intrabitoneal injection of estradiol benzoate combined with progesterone.The rats were randomly divided into control group(normal rats were intragastric administration with 2 ml 0.9%sodium chloride solution),model group(uterine fibroids rats were intragastric administration with 2 ml 0.9%sodium chloride solution),tamoxifen group(uterine fibroids rats were intragastric administration with 1.70 mg/kg tamoxifen)and levonorgestrel group(uterine fibroids rats were intragastric administration with 0.1 mg/kg levonorgestrel)and combination group(tamoxifen combined with levonorgestrel intragastric administration in uterine fibroid rats),6 rats in each group were given continuous intragastric administration for 30 days.Serum levels of estradiol(E2),progesterone,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)were detected by ELISA.Uterine coefficient,length of left and right cervical horn and maximum diameter of uterine horn were measured.The structure and endometrial thickness of uterus were observed by HE staining.The expressions of Wnt5b andβ-catenin protein in uterine tissue were detected by Western blot.Results:Compared with the control group,the serum levels of E2,progesterone,FSH and LH in the model group were increased(all P<0.05).The serum levels of E2,progesterone,FSH and LH in combination group were lower than those in tamoxifen group and levonorgestrel group(all P<0.05).Uterine coefficient,length of left and right cervical horn,maximum diameter of uterine horn and endometrial thickness in model group were increased compared with those in control group(all P<0.05).Uterine coefficient,length of left and right cervical corners,maximum diameter of uterine horn and endometrial thickness in combination group were lower than those in tamoxifen and levonorgestrel groups(all P<0.05

关 键 词：子宫肌瘤 他莫昔芬 左炔诺孕酮 WNT通路 Β-连环蛋白 大鼠 

分 类 号：R-33[医药卫生]