来曲唑对SD大鼠子宫内膜异位症模型的影响及其机制OA
Effect and mechanism of letrozole on endometriosis models in SD rats
目的 探讨来曲唑对SD大鼠子宫内膜异位症(endometriosis,EMs)模型的影响及其可能的分子生物机制.方法选取8周龄雌性SD大鼠30只,采用自体子宫移植建立EMs模型,随机分为模型组、来曲唑组和卵巢去势组,每组10只.各组干预4周后,ELISA测定血清雌二醇(E2)、睾酮、促卵泡刺激素(FSH)和促黄体生成素(LH)水平;游标卡尺测量EMs病灶体积并计算缩小率;HE染色检测SD大鼠EMs病灶的组织学改变;免疫组织化学和RT-qPCR检测SD大鼠EMs病灶β-catenin、c-Myc、Cyclin D1、Bcl-2和Bax蛋白和mRNA表达.结果 与模型组相比,来曲唑组和卵巢去势组病灶体积明显减小(P<0.05);来曲唑组和卵巢去势组比较差异无统计学意义(P>0.05).来曲唑组和卵巢去势组病灶腺上皮萎缩,间质纤维化加重.与模型组相比,来曲唑组和卵巢去势组E2水平均显著降低(P<0.05),且卵巢去势组的E2水平低于来曲唑组(P<0.05).与模型组相比,来曲唑组睾酮水平升高,而卵巢去势组睾酮水平降低(均P<0.05).与模型组相比,来曲唑组和卵巢去势组FSH和LH水平均显著升高(P<0.05),且卵巢去势组FSH和LH水平显著高于来曲唑组(P<0.05).与模型组比较,来曲唑组和卵巢去势组β-catenin的亚细胞定位发生改变;同时,来曲唑组和卵巢去势组c-Myc、Cyclin D1和Bcl-2蛋白和mRNA表达明显降低,Bax蛋白和mRNA表达明显升高(P<0.05),来曲唑组各指标均略小于卵巢去势组,但组间差异无统计学意义(P>0.05).结论 来曲唑可明显降低EMs大鼠模型E2水平,抑制EMs病灶生长,疗效与卵巢去势相当,其作用机制可能与抑制Wnt/β-catenin信号通路相关.
Objective To investigate the effect of letrozole on a rat model of endometriosis(EMs)and its potential molecular biological mechanism.Methods Thirty 8-week-old female SD rats were used to establish endometriosis models via autologous uterine trans-plantation,and then randomly divided into three groups:model group,letrozole group,and ovariectomy group,with 10 rats in each group.After four weeks of intervention,serum levels of estradiol(E2),testosterone,follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured by ELISA.The volume of endometriotic lesions was measured using Vernier calipers,and the shrinkage rate was calculated.Histological changes of endometriotic lesions were observed by HE staining.Protein and mRNA expressions of β-catenin,c-Myc,Cyclin D1,Bcl-2,and Bax in endometriotic lesions were detected by immunohistochemistry and RT-qPCR.Results Compared with model group,the lesion volumes in letrozole group and ovariectomy group significantly reduced(P<0.05),while there was no statistically significant difference between letrozole group and ovariectomy group(P>0.05).Glandular epithelial atrophy was observed,and stromal fibrosis was aggravated in letrozole group and ovariectomy group.Compared with model group,serum E2 level significantly decreased in letrozole group and ovariectomy group(P<0.05),and E2 level in ovariectomy group was lower than that in letrozole group(P<0.05).Compared with model group,testosterone level increased in letrozole group but decreased in ovariectomy group(P<0.05);FSH and LH levels were significantly elevated in both tletrozole group and ovariectomy group,and they were signifi-cantly higher in ovariectomy group than in letrozole group(P<0.05).Compared with model group,the subcellular localization of β-catenin was altered in both letrozole group and ovariectomy group,meanwhile,the protein and mRNA expressions of c-Myc,Cyclin D1,and Bcl-2 were significantly down-regulated while the expression of Bax was significantly up-regulated in letrozole group and ova-riectomy group(all P<0.05),and all indicators were numerically lower in letrozole group than in ovariectomy group,but there was no statistical difference(P>0.05).Conclusion Letrozole can significantly reduce E₂ level and inhibit endometriotic lesion growth in a rat model of endometriosis,with efficacy comparable to ovariectomy,which may be related to the inhibition of Wnt/β-catenin signaling pathway.
侯晓芬;高艳萍;王兴旺;李汇;梁铭;罗亚军;陈琛;李雅清;刘英;段玉坤
大同市妇幼保健院,大同市第一人民医院妇科,大同 037009||围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地大同市妇幼保健院,大同市第一人民医院妇科,大同 037009||围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地大同市妇幼保健院,大同市第一人民医院妇科,大同 037009||围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地大同市妇幼保健院,大同市第一人民医院妇科,大同 037009围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地||大同市妇幼保健院,大同市第一人民医院科研实验室围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地||大同市妇幼保健院,大同市第一人民医院科研实验室大同市妇幼保健院,大同市第一人民医院病理科围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地||大同市妇幼保健院,大同市第一人民医院科研实验室围绝经期激素代谢性疾病厅市共建山西省重点实验室培育基地||大同市妇幼保健院,大同市第一人民医院科研实验室大同市妇幼保健院,大同市第一人民医院妇科,大同 037009
医药卫生
子宫内膜异位症来曲唑β-catenin卵巢去势细胞凋亡
endometriosisletrozoleβ-cateninovariectomycell apoptosis
《山西医科大学学报》 2026 (4)
445-453,9
大同市应用基础研究计划项目(2022062,2022063)
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