电针调控类固醇激素及其受体改善PCOS大鼠着床障碍的机制研究

Polycystic ovary syndrome (PCOS) is a complicated disease caused female infertility. The endometrium from PCOS is a target tissue for abnormal steroid environment, and exert key physiological function depending on steroids and their receptors. PCOS female rats were studied to verify the regulatory mechanism of electro-acupuncture on endometrial receptivity excluding the factor of embryo by pseudopregnancy model and in vitro embryo transfer. The differences in steroid hormone levels, embryo implantation rate and farrowing rate were compared in control group and PCOS group, to explore the mechanism of electro-acupuncture mediated by steroid receptors. To analyze the role of electro-acupuncture on improving endometrial receptivity in PCOS using molecular biological techniques and the mechanism on steroid receptors as well as their co-activators and co-repressors. Based on previous researches on the effect of electro-acupuncture on PCOS rat model and the mechanism of embryo implantation, to clarify the therapeutic mechanism of electro-acupuncture on improving implantation dysfunction in PCOS. This project scientifically illustrated the etiological study on endometrial receptivity defects in PCOS and provided important theoretical foundation for the research of electro-acupuncture improving the rates of embryo implantation and pregnancy.

多囊卵巢综合征（PCOS）是引起女性不孕的一种复杂性疑难疾病，其子宫内膜是类固醇激素异常分泌作用的靶向组织，主要通过类固醇激素及其受体的相互作用来发挥其重要的生理功能。本项目以PCOS模型雌性大鼠为研究对象，利用假孕模型和体外胚胎移植技术排除胚胎因素从子宫内膜容受性单方面验证电针的调控机制，比较其在对照组和PCOS模型组中对类固醇激素水平、胚胎着床率及产仔率的差异，探讨电针治疗后经类固醇激素受体介导发挥的作用机制。利用分子生物学实验技术手段，分析电针对PCOS子宫内膜容受性的改善作用和对类固醇激素受体及其共激活/共抑制因子的调控机制。基于前期电针对PCOS模型系统的调控以及胚胎着床机制的研究结果，阐明电针改善PCOS着床障碍的疗效机制。本研究对PCOS子宫内膜容受性缺陷的病因学研究进行了科学阐述，为电针提高PCOS胚胎着床率、妊娠率的研究提供了重要的理论依据。

多囊卵巢综合征( Polycystic ovary syndrome, PCOS) 是育龄期女性中最常见的一种内分泌和代谢性疾病，以高雄激素血症、排卵障碍及多囊性卵巢形态这三种表型特点为基本特征。而且，PCOS女性由于无排卵性不孕及反复流产严重影响了女性的生殖能力。即使PCOS女性恢复排卵，其生殖能力也不佳。研究已知PCOS女性妊娠失败部分原因是因为子宫内膜功能紊乱。子宫内膜在类固醇激素作用下其生长和发育发生周期改变。雌激素、孕激素、雄激素通过其特异性受体介导作用于子宫内膜，共同为成功妊娠维持一个良好的微环境。针灸治疗妇科疾病已有千年的历史。现在已经成为不孕症治疗的一种常见替代疗法。本研究旨在揭示电针经类固醇激素受体介导对PCOS大鼠子宫内膜容受性的作用机制。与对照组相比，PCOS大鼠出现动情周期紊乱、体重增加、多囊样卵巢改变、糖耐量异常、雄激素过多表现，经电针治疗后，上述异常均有所改善。结果证实电针治疗能够改善PCOS大鼠动情周期紊乱和多囊卵巢形态，恢复其排卵功能，改善PCOS大鼠糖耐量异常，降低雄激素水平。本研究从分子生物学机制方面证实电针通过调控类固醇激素受体途径改善子宫内膜容受性。通过免疫组化和Western Blot实验研究发现，PCOS大鼠子宫内膜中ER、PR、AR以及共激活子ARA70表达异常，说明PCOS大鼠子宫内膜在类固醇激素作用下介导的受体蛋白表达水平改变影响了子宫内膜容受性，电针通过调控类固醇激素及其受体改善子宫内膜容受性，提高PCOS大鼠生殖功能。