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目的探讨GATA-4在多囊卵巢综合征(PCOS)发病机制中的作用,并为来曲唑诱导的PCOS模型的应用提供一定的理论依据。方法 40只雌性SD大鼠随机分为模型组和对照组,模型组来曲唑1mg/(kg.d)溶于10g/L羧甲基纤维素(CMC)中,连续灌服21d;对照组给予同体积的溶剂(CMC)灌服。放射免疫法测定大鼠血清性激素水平;HE染色观察卵巢组织学变化;免疫组织化学、实时定量PCR和免疫印迹法检测GATA-4在卵巢组织中的表达。结果模型组血清睾酮(T)、促黄体生成素(LH)、促卵泡刺激素(FSH)浓度显著增高,雌二醇(E2)、孕酮(P)浓度降低。与对照组比较,模型组可见囊状扩张卵泡明显增多,卵巢白膜增厚,黄体数量明显减少。模型组卵巢窦前卵泡和窦状卵泡颗粒细胞GATA-4表达显著增强,卵巢组织中GATA-4mRNA及蛋白表达水平均显著高于对照组(P<0.05)。结论卵泡颗粒细胞GATA-4表达异常增高与多囊卵巢综合征的发生密切相关。来曲唑诱导的PCOS动物模型是研究PCOS病理机制的一种理想的动物模型。
Objective To investigate the role of GATA-4 in the pathogenesis of polycystic ovary syndrome (PCOS) and to provide a theoretical basis for the application of letrozole-induced PCOS model. Methods Forty female SD rats were randomly divided into model group and control group. Letrozole 1 mg / (kg · d) was dissolved in 10 g / L carboxymethylcellulose (CMC) for 21 days. The control group Give the same volume of solvent (CMC) fed. The levels of serum sex hormones were determined by radioimmunoassay. The ovarian histological changes were observed by HE staining. The expression of GATA-4 in ovarian tissue was detected by immunohistochemistry, real-time quantitative PCR and Western blotting. Results The levels of serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in model group were significantly increased while the concentrations of estradiol (E2) and progesterone (P) were decreased. Compared with the control group, the model group showed a significant increase in cystic dilated follicles, thickening of the albuginea ovary, significantly reduced the number of corpus luteum. The expression of GATA-4 in ovarian preantral follicles and sinusoidal granulosa cells in model group was significantly increased, and the levels of GATA-4 mRNA and protein in ovarian tissue were significantly higher than those in control group (P <0.05). Conclusion The abnormal expression of GATA-4 in granulosa cells is closely related to the occurrence of PCOS. Letrozole induced PCOS animal model is an ideal animal model of PCOS pathology.