脱氢表雄酮联合高脂饮食诱导建立小鼠多囊卵巢综合征模型的研究

Establishment of mouse model of polycystic ovary syndrome induced by dehydroepiandrosterone combined with high-fat diet

目的通过脱氢表雄酮(DHEA)联合高脂饮食及单纯DHEA构建多囊卵巢综合征(PCOS)小鼠模型,模拟PCOS生殖及代谢特征,探究更理想的PCOS小鼠模型构建方法。方法选取30只21日龄雌性C57BL/6J小鼠,随机分为对照组、DHEA组及DHEA联合高脂饮食组(DHEA+HFD组),每组各10只,通过小鼠体重变化、动情周期、卵巢形态、血清生殖激素水平、糖脂代谢等指标进行模型评价。结果3组造模后的第12、15、18、21天,DHEA+HFD组和DHEA组小鼠的体重增加,均显著高于对照组(P<0.01),且DHEA+HFD组体重较DHEA组显著增加(P<0.01)。对照组的阴道涂片可见规律的排卵周期,DHEA+HFD组及DHEA组均多见大片不规则形状的鳞状上皮细胞。HE染色结果显示,DHEA+HFD组和DHEA组均观察到卵巢表面呈多囊样改变,黄体数量少于对照组,卵泡颗粒细胞层数减少。与对照组比较,DHEA组和DHEA+HFD组小鼠空腹血糖(FPG)、空腹血胰岛素(FINS)、总胆固醇(TCHO)、高密度脂蛋白(HDL)、谷草转氨酶(AST)水平均显著升高(P均<0.05)。与DHEA组比较,DHEA+HFD组稳态模型评估胰岛素抵抗指数(HOMA-IR)、TCHO、HDL、AST均显著升高(P均<0.01),且肝脏脂质蓄积增加。结论DHEA联合高脂饮食及DHEA均成功构建出小鼠PCOS模型,但DHEA联合高脂饮食较DHEA构建的PCOS模型生殖与代谢特征更明显,是一种理想的PCOS动物造模方法。

Objective:To establish the mouse model of polycystic ovary syndrome(PCOS)induced by dehydroepiandrosterone(DHEA)combined with high-fat diet or DHEA alone for simulating the reproductive and metabolic characteristics of PCOS,in order to find a more ideal method for establishing PCOS mouse model.Methods:Thirty 21-day female C57BL/6J mice were selected and randomly divided into control group,DHEA group,and DHEA combined with high-fat diet(DHEA+HFD)group,10 mice for each group.Body weight,estrous cycle,ovarian morphology,serum sex hormone levels and glycolipid metabolism indicators were recorded and evaluated.Results:On the 12^(th),15^(th),18^(th) and 21^(st) days after modeling,the weight gain in DHEA+HFD group and DHEA group was significantly higher than that of the control group(P<0.01),and the weight in DHEA+HFD group was significantly higher than that in DHEA group(P<0.01).Regular ovulation cycles were observed in vaginal smears of the control group.Large irregular squamous epithelial cells were found in DHEA+HFD group and DHEA group.HE staining showed that polycystic changes were observed on the ovarian surface in DHEA+HFD group and DHEA group;the number of corpus luteum was less than that in the control group,and the number of layers of follicular granulosa cells decreased.Compared with the control group,the fasting plasma glucose level(FPG),fasting blood insulin(FINS),total cholesterol(TCHO),high-density lipoprotein(HDL)and aspartate aminotransferase(AST)of the two experimental groups were significantly higher than those of the control group(P<0.05).Compared with the DHEA group,insulin resistance index(HOMA-IR),TCHO,HDL and AST in the DHEA+HFD group were significantly increased(P<0.01),and lipid accumulation in the liver was increased.Conclusions:DHEA combined with high-fat diet or DHEA alone can successfully establish PCOS mouse model.However,the reproductive and metabolic abnormalities of mice induced by DHEA combined with high fat diet were more significant than those induced by DHEA alone,which is an ideal method for establishing PCOS animal.