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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 expose mid-pregnancy female rats to hyperandrogenism and to observe the serum hormone levels and the expression of 17a-hydroxylase (CYP17) in ovarian tissues of female offspring after early metformin treatment. Methods: Female Wistar rats, pregnant for 16-18 days, were injected subcutaneously with testosterone propionate on the back of the neck for 3 consecutive days. Pregnant mice were given metformin 2 days after giving birth for 14 consecutive days. Female pups were grown to adulthood as experimental subjects, serum hormone levels were observed, and immunohistochemistry and Western blotting were used to detect the expression of CYP17 in ovarian tissues. Results: (1) The ovaries of female mice in the second trimester of pregnancy were changed to polycystic, and the levels of testosterone and LH were significantly increased (P <0.05), and the levels of FSH and INS were not significantly changed. In the ovarian tissues CYP17 expression was significantly enhanced (P <0.05). (2) After the female offspring were treated with metformin, the changes of polycystic ovary were relieved, the levels of testosterone and LH decreased, and the expression of CYP17 in ovary decreased. CONCLUSION: Pregnant females injected with testosterone propionate in the second trimester showed that the female mice exhibited hyperandrogenism. High LH and ovarian cystic changes were consistent with the characteristics of human PCOS. Metformin could improve the expression of CYP17 in the ovary by regulating the level of serum hormone and ovarian CYP17 The clinical symptoms of intrauterine growth hormone pups.