D-半乳糖联合脱氢表雄酮诱导小鼠多囊卵巢综合征模型

Establishment of a mouse model of polycystic ovary syndrome induced by D-galactose combined with dehydroepiandrosterone

目的研究D-半乳糖联合脱氢表雄酮(DHEA)诱导小鼠多囊卵巢综合征(PCOS)模型的建立方法。方法 20周龄雌性ICR小鼠随机分为正常对照组、DHEA组、D-半乳糖组和D-半乳糖联合脱氢表雄酮组(D+D联合组),分别给予溶剂注射、70mg/kg DHEA颈背部皮下注射、200mg/kg D-半乳糖腹腔注射,以及D-半乳糖联合DHEA分别腹腔注射及颈背部皮下注射,每天1次,连续21d。监测小鼠饮食和体重变化;取血测定小鼠空腹血糖值;观察小鼠动情周期排卵情况以及取卵巢组织并做HE染色,观察小鼠卵巢组织结构及形态变化。结果 D+D联合组、DHEA组、D-半乳糖组与对照组相比进食量均有所降低,且D+D联合组、DHEA组显著低于对照组(P<0.05)。D+D联合组、DHEA组与对照组相比体重稍有增高,而D-半乳糖组与对照组相比体重稍有降低,但均无统计学差异(P>0.05)。各造模组动情周期紊乱,表现为持续动情间期或动情后期,D+D联合组的变化更为明显。D+D联合组能够明显诱发卵巢卵泡发生闭锁及囊状扩张,91.7%(11/12)小鼠可见此变化,与PCOS患者卵巢病理改变非常相似,而单纯应用D-半乳糖或DHEA所致小鼠单侧或双侧卵巢囊肿及多囊性变化不甚明显,均只有50.0%(6/12)小鼠可见此变化。结论 D-半乳糖联合DHEA可诱导小鼠PCOS模型,其效果优于非联合组。

Objective:To establish of a mouse model of polycystic ovary syndrome induced by D-galactose combined with dehydroepiandrosterone(DHEA).Methods:The female ICR mice with 20 weeks old were randomly divided into normal control group,DHEA group,D-galactose group and D-galactose combined with DHEA group(D+D group).The mice were given solvent injection,70 mg/kg DHEA subcutaneous injection on the nape back,200 mg/kg D-galactose intraperitoneal injection,and D-galactose subcutaneous injection combined with DHEA intraperitoneal injection for each group respectively,once daily for 21 consecutive days.The changes in diet and weight of mice were monitored.Blood glucose was measured and estrous cycle was observed,finally ovarian tissues were taken for HE staining to observe the changes of the structure and morphology in ovarian tissue.Results:The food intake of mice in D-galactose combined with DHEA group,DHEA group and D-galactose group were all decreased compared with the control group,and the food intake in D-galactose combined with DHEA group and DHEA group were significantly lower than the control group(P<0.05).Compared with the control group,the mice in D-galactose combined with DHEA group and the DHEA group had a slight increase in weight,while the D-galactose group had a slight decrease in weight,but the differences were not significant(P >0.05).In the experimental group,the estrous cycle was disordered,and the change in D-galactose combined with DHEA group was more obvious.The D-galactose combined with DHEA can significantly induce ovarian follicle atresia and cystic dilatation,which were seen in 91.7%of mice(11/12)and was similar to the pathological changes of PCOS patients’ovary.The changes of unilateral or bilateral ovarian cysts and poly-cysts in mice induced by D-galactose or DHEA only were not obvious,and only 50%of mice(6/12)showed the changes.Conclusions:D-galactose combined with DHEA can induce polycystic ovary syndrome in mice,and the effect is better than the non-combined group.