炔雌醇环丙孕酮对多囊卵巢综合征大鼠卵巢组织形态影响的研究

Morphologic and ultrastructure changes in ovaries of polycystic ovary syndrome model rats treated with ethinylestradiol and cyproterone acetate tablets

目的观察炔雌醇环丙孕酮对多囊卵巢综合征(PCOS)模型大鼠卵巢组织形态和超微结构的影响。方法应用来曲唑造模法建立PCOS大鼠模型,随机分为正常对照组、PCOS模型组、炔雌醇环丙孕酮组,应用放射免疫法测定各组大鼠性激素水平、光镜观察大鼠卵巢组织形态改变、电子显微镜观察卵巢超微结构。结果①应用来曲唑干预21d后,PCOS模型大鼠血清黄体生成素(LH)、睾酮和卵泡刺激素(FSH)的水平明显高于正常对照组,而雌二醇和孕酮水平低于对照组(P<0.01),提示造模成功。药物干预后,与PCOS模型组比较,炔雌醇环丙孕酮组大鼠血清LH、FSH和睾酮水平下降,血清雌二醇、孕酮水平升高,差异有统计学意义(P<0.05)。②光镜观察:PCOS组大鼠卵巢组织呈多囊性改变,未见成熟卵泡及黄体生成;对照组卵巢组织可见不同发育阶段的卵泡及黄体的生成;炔雌醇环丙孕酮组较PCOS组大鼠有所改善,可见成熟卵泡及黄体的生成。③电镜观察:PCOS组比正常对照组大鼠卵巢电镜下见颗粒细胞出现凋亡形态特征,卵泡膜细胞较多,内可见脂滴明显增多;炔雌醇环丙孕酮组大鼠卵巢镜下颗粒细胞凋亡所特有的超微结构变化明显改善,可见正常的颗粒细胞和卵丘,线粒体增多,有大量滑面内质网;卵泡膜细胞凋亡明显增多。结论用来曲唑建立PCOS大鼠模型是一种较为理想的方法;炔雌醇环丙孕酮能够从形态学上改善PCOS大鼠的卵巢组织,恢复排卵功能。

Objective To investigate morphologic and ultrastructure changes in ovaries of polycystic ovary syndrome （PCOS） model rats treated with ethinylestradiol and cyproterone acetate tablets. Methods Female rat models of PCOS were established with letrozole and randomly divided into three groups （control group, PCOS model group, ethinylestradiol and cyproterone acetate tablets treated group）. The serum levels of sex hormone were examined by radioimmunoassay. The pathohistologic changes in rat ovarian structure were observed by hematoxylin-eosin （HE） staining in three groups, The ultrastructure of the rat ovary in the three groups was studied by transmission electron microscope. Results ①The serum luteinizing hormone （LH）, testosterone （T） and follicle stimulating hormone （FSH） in letrozole experimental group were significantly higher than those in control group （P0.01）. The serum estradiol （E2） and progesterone （P） in experimental group was significantly lower than the control group （P0.01）. Compared with PCOS model group,the serum levels of LH, FSH, T in the ethinylestradiol and cyproterone acetate tablets treated rats were lower and the levels of E2, P were higher after drug intervention （P0.05）. ②The ovarian tissue of the PCOS model rats showed multiple cysts and no mature follicles and luteinizing under optical microscope. In the control group, ovarian tissue can be seen at different development stages of follicle and corpus luteum formation. Ethinylestradiol and cyproterone acetate tablets treated group showed improved mature follicle and corpus luteum formation under optical microscope. ③Compared with the normal control group, the morphological characteristics of apoptosis in granulosa cells and theca cells are more visible with the significantly increased lipid droplets under transmission electronic microscope in the PCOS model group in rats. In the ethinylestradiol and cyproterone acetate tablets treated group, microscopic ultrastructure characteristic of ovarian granulosa cell apoptosis was significantly improved. Conclusion ①The rat model induced with letrozole is one of suitable models for PCOS study. ②The ethinylestradiol and cyproterone acetate tablets may improve the ovarian morphology of PCOS and restore ovulation in rat models.