出生早期使用二甲双胍对宫内高雄激素化仔鼠成年后卵巢CYP17的影响  

Expression of CYP17 in ovarian tissue of adult rat model with hyperandrogenism in uterus and treatment by metformin in newborn

作　　者：樊佳丽[1,2] 段涛[1,2] 周倩[1] 

机构地区：[1]同济大学附属第一妇婴保健院,上海200040 [2]同济大学医学院,上海200092

出　　处：《现代妇产科进展》2012年第12期941-944,共4页Progress in Obstetrics and Gynecology

基　　金：上海市卫生系统新百人计划资助(No:XBR2011064);上海市科委实验动物专项基金资助(No:11140901900);教育部高等学校博士点基金(No:2011007210005)

摘　　要：目的:使孕中期雌鼠暴露于高雄激素状态,观察其雌性子代在出生早期使用二甲双胍后,血清激素水平及卵巢组织中17a-羟化酶(CYPl7)表达情况。方法:选择孕16～18天的Wistar雌性大鼠,在颈背部皮下注射丙酸睾丸酮,连续3天。孕鼠分娩后第2天予以二甲双胍灌胃,连续14天。雌仔鼠生长至成年后作为实验对象,观察血清激素水平,运用免疫组化及蛋白印迹方法,检测卵巢组织中CYPl7蛋白的表达。结果:(1)孕中期雌鼠经雄激素处理后,所生雌鼠卵巢呈多囊样改变,睾酮、LH水平显著升高(P<0.05),FSH、INS水平没有明显变化;卵巢组织中CYP17表达显著增强(P<0.05)。(2)子代雌鼠予以二甲双胍干预后卵巢多囊样改变缓解,睾酮、LH水平下降;卵巢组织中CYP17表达减弱。结论:孕中期雌鼠注射丙酸睾丸酮,所生雌鼠表现为高雄激素血症、高LH,卵巢囊性化改变符合人类PCOS特征,二甲双胍可通过调节血清激素水平和卵巢内CYPl7的表达改善宫内高雄激素化仔鼠的临床症状。Objective ：To construct polycystic ovary syndrome（PCOS） rat model by mater- hal exposure to excess testosterone ,examine the CYP17 and metabolism in the rat models after trea- ted by metformin in newborn. Methods ：Wistar female rats were randomly divided into model group and control group. On days 16 ~ 18 of pregnancy ,wistar female rats were injected S. C. with testoster- one propionas 2.5 mg or sesame oil daily for 3 consecutive days. Pregnant rats after delivery 2 days were gavaged by metformin 450mg/（ kg ~ d） and saline for 14 consecutive days. Adult female off- springs were studied. Serum concentrations of sex hormones luteinizing hormone ,Follicle-stimulating hormone ,Testosterone ,insulin were measured. CYP17 protein expression in ovary were determined by immunohistochemistry and Western blot. Result： （ 1 ） The female rats that were prenatally androg- enized had polycystic ovary. Serum levels of testosterone, luteinizing hormone were significantly higher. The insulin levels and Follicle-stimulating hormone had not changed. Western blot showed that the expression of CYP17 in model ovarian tissues were higher. （2） The prenatally androgenized female rats that were treated by metformin in newborn had normal ovary. Serum hormone levels and the expression of CYP17 returned to normal. Conclusion： Prenatally androgenized female rats exhibi- ted hyperandrogenism, high lnteinizing hormone and polycystic ovary, which is coincident with the characteristics of human PCOS. Mefformin by adjusting the serum hormone levels and ovarian CYP17 expression played a role in improve the clinical symptoms of prenatal androgen mice.

关 键 词：多囊卵巢综合征 丙酸睾酮 二甲双胍 类固醇17-α-羟化酶 基因 CYP17 Wistar雌性大鼠 

分 类 号：R711.75[医药卫生—妇产科学]