中华小儿外科杂志
中華小兒外科雜誌
중화소인외과잡지
CHINESE JOURNAL OF PEDIATRIC SURGERY
2011年
11期
855-858
,共4页
马峥%蒋君涛%朱英坚%洪艳%刘国华
馬崢%蔣君濤%硃英堅%洪豔%劉國華
마쟁%장군도%주영견%홍염%류국화
邻苯二甲酸二丁酯%尿道下裂%睾酮%雄激素受体%成纤维细胞生长因子8
鄰苯二甲痠二丁酯%尿道下裂%睪酮%雄激素受體%成纖維細胞生長因子8
린분이갑산이정지%뇨도하렬%고동%웅격소수체%성섬유세포생장인자8
Di-n-butyl phthalate%Hypospadias%Testosterone%Androgen receptors%Fibroblast
目的 通过检测邻苯二甲酸二丁酯(DBP)孕期染毒所致尿道下裂雄性大鼠仔鼠睾酮(T)、雄激素受体(AR)及成纤维细胞生长因子8(FGF8)的表达,研究DBP干预雄激素依赖性FGF8通路致尿道下裂发生的相关机制.方法 20只孕鼠随机分为两组,孕14～18 d,分别予大豆油及DBP 750 mg·kg-1 ·d-1灌胃.仔鼠出生第一天,统计仔鼠出生数、尿道下裂发生率.第七天时,称量雄性仔鼠体重,拍摄尿道下裂图片,分别取两组中尿道下裂仔鼠及正常仔鼠血清和生殖结节(GT),用放射免疫法检测仔鼠血清睾酮含量；用定量逆转录聚合酶链式反应(Real-time quantitative PCR)及WesternBlot检测AR与FGF8表达水平.结果 染毒组及对照组产仔数分别为9.10±0.99和12.60±1.26,仔鼠体重(g)分别为9.53±0.12和11.93±0.15,DBP的生殖毒性作用导致染毒组孕鼠产仔数及仔鼠体重明显减少(P＜0.05),雄性仔鼠尿道下裂发生率为37.2％.染毒组仔鼠血清睾酮浓度(41.85±8.38) ng/L、生殖结节中AR0.404±0.040及FGF 80.036±0.004的表达均明显低于对照组睾酮浓度( 107.40±24.28) ng/L、AR表达1.669±0.124及FGF8表达0.168±0.004(P＜0.05).结论 DBP对孕鼠有明显的生殖毒性,DBP通过干预雄激素依赖性FGF8信号通路,导致尿道下裂的发生.
目的 通過檢測鄰苯二甲痠二丁酯(DBP)孕期染毒所緻尿道下裂雄性大鼠仔鼠睪酮(T)、雄激素受體(AR)及成纖維細胞生長因子8(FGF8)的錶達,研究DBP榦預雄激素依賴性FGF8通路緻尿道下裂髮生的相關機製.方法 20隻孕鼠隨機分為兩組,孕14～18 d,分彆予大豆油及DBP 750 mg·kg-1 ·d-1灌胃.仔鼠齣生第一天,統計仔鼠齣生數、尿道下裂髮生率.第七天時,稱量雄性仔鼠體重,拍攝尿道下裂圖片,分彆取兩組中尿道下裂仔鼠及正常仔鼠血清和生殖結節(GT),用放射免疫法檢測仔鼠血清睪酮含量；用定量逆轉錄聚閤酶鏈式反應(Real-time quantitative PCR)及WesternBlot檢測AR與FGF8錶達水平.結果 染毒組及對照組產仔數分彆為9.10±0.99和12.60±1.26,仔鼠體重(g)分彆為9.53±0.12和11.93±0.15,DBP的生殖毒性作用導緻染毒組孕鼠產仔數及仔鼠體重明顯減少(P＜0.05),雄性仔鼠尿道下裂髮生率為37.2％.染毒組仔鼠血清睪酮濃度(41.85±8.38) ng/L、生殖結節中AR0.404±0.040及FGF 80.036±0.004的錶達均明顯低于對照組睪酮濃度( 107.40±24.28) ng/L、AR錶達1.669±0.124及FGF8錶達0.168±0.004(P＜0.05).結論 DBP對孕鼠有明顯的生殖毒性,DBP通過榦預雄激素依賴性FGF8信號通路,導緻尿道下裂的髮生.
목적 통과검측린분이갑산이정지(DBP)잉기염독소치뇨도하렬웅성대서자서고동(T)、웅격소수체(AR)급성섬유세포생장인자8(FGF8)적표체,연구DBP간예웅격소의뢰성FGF8통로치뇨도하렬발생적상관궤제.방법 20지잉서수궤분위량조,잉14～18 d,분별여대두유급DBP 750 mg·kg-1 ·d-1관위.자서출생제일천,통계자서출생수、뇨도하렬발생솔.제칠천시,칭량웅성자서체중,박섭뇨도하렬도편,분별취량조중뇨도하렬자서급정상자서혈청화생식결절(GT),용방사면역법검측자서혈청고동함량；용정량역전록취합매련식반응(Real-time quantitative PCR)급WesternBlot검측AR여FGF8표체수평.결과 염독조급대조조산자수분별위9.10±0.99화12.60±1.26,자서체중(g)분별위9.53±0.12화11.93±0.15,DBP적생식독성작용도치염독조잉서산자수급자서체중명현감소(P＜0.05),웅성자서뇨도하렬발생솔위37.2％.염독조자서혈청고동농도(41.85±8.38) ng/L、생식결절중AR0.404±0.040급FGF 80.036±0.004적표체균명현저우대조조고동농도( 107.40±24.28) ng/L、AR표체1.669±0.124급FGF8표체0.168±0.004(P＜0.05).결론 DBP대잉서유명현적생식독성,DBP통과간예웅격소의뢰성FGF8신호통로,도치뇨도하렬적발생.
Objective To evaluate the expression of Testosterone、Androgen Receptor and FGF8 in genital tubercle (GT) of hypospadiac male rats following in utero exposure to DBP,to investigate molecular mechanism of DBP on androgen related FGF8 pathway.Methods Twenty pregnant rats were randomly divided into 2 groups and given DBP by gastric intubation at a dose of 0,750 mg/kg from gestation day(GD) 14 to GD18.On postnatal day (PND) 1,male pups were examined for hypospadias.On PND7,the body weight of male pups were measured and the gross image of hypospadiac genitalia were checked.Real-time quantitative PCR and WesternBlot were used to evaluate expression of AR and FGF8 in the GT.Radio-immunoassay was used to evaluate testosterone concentration in the serum of hypopadiac rats.Results The number and body weight of live pups in the DBP group (9.10 ± 0.99;9.53 ± 0.12 g) was significantly lower when compared with the control group(12.60 ±1.26; 11.93 ± 0.15 g) ( P ＜ 0.05 ),and the incidence of hypospadias was 37.2 ％.Significantly decreased expression of AR and FGF8 were also found in both mRNA and protein levels in the DBP group(AR:0.404 ± 0.040; FGF8:0.036 ± 0.004),when compared with the control group(AR:1.669± 0.124; FGF8:0.168 ± 0.004) ( P ＜ 0.005 ).The testosterone concentration of DBP treating group (41.85 ± 8.38 ng/L) was also lower than control group( 107.40 ± 24.28 ng/L)(P＜0.05).Conclusions Toxic effects of DBP to pregnant rats were seen.The occurrence of hypospadias may be related to the interference on androgen related FGF8 pathway by DBP.
