大豆异黄酮诱导小鼠尿道下裂模型的建立

Establishment of a mouse model of hypospadias induced by soy isoflavone

目的应用大豆异黄酮孕晚期染毒诱导子代雄鼠尿道下裂的建立,为雌激素致尿道下裂的分子作用机制提供进一步研究的基础。方法45只孕鼠随机分成5组,在孕12-17d连续6d各组每晨9点分别灌胃生理盐水0.2ml/d(A组)、己烯雌酚0.5mg/(kg.d)(B组)、大豆异黄酮100mg/(kg.d)(C组)、300mg/(kg.d)(D组)、900mg/(kg.d)(E组),出生时观察小鼠病死率,出生后4周观察小鼠有无尿道下裂。结果A,B,C,D,E各组平均病死率分别为2.0%,18.0%,3.8%,5.4%,10.0%。A,B,C,D,E组子代尿道下裂发生率分别为0%(0/80),28.2%(11/39),0%(0/76),0%(0/67),19.2%(10/52)。E组子代尿道下裂发生率与A,C,D组比较有统计学差异(P<0.05)。E组子代尿道下裂发生率与B组比较无统计学差异。结论应用昆明种小鼠从孕12d开始给予大豆异黄酮900mg/(kg.d)灌胃,连续给药6d,成功建立小鼠先天性尿道下裂模型。

Objective To establish a hypospadias mouse model by maternal exposure to soy isoflavone during late pregnancy, and to explore the molecular mechanism of hypospadias. Methods Forty-five pregnancy mice were randomly divided into five groups. The mice were injected with 0.2 ml/d sodium chloride（group A） ,0.5 mg/（kg·d） diethylstilbestrol（group B） ,soy isoflavone of 100mg/ （kg·d） （group C）,300 mg/（kg·d） （group D）,900 mg/（kg·d） （group E）from growth day 12 to day 17,respectively.At the delivery day,mortality was recorded. Urethra was examined at postnatal day 28. Results Mortalities in groups A, B,C,D,E were 2.0 %, 18.0 %, 3.8 %, 5.4 %, 10.0 % at the delivery day, respectively. Hypospadias rates in groups B and E were significantly higher than in groups A, C, D at postnatal day 28 （P 〈 0.05）, but there was no significant difference between groups E and B. Conclusion Kunruing mice can be used to successfully build up hypospadias model after gavage of soy isofiavone for 6 d with a dosage of 900 mg/（kg·d）.