摘要
目的在邻苯二甲酸二(2-乙基)己酯[di-(2-ethylhexyl)phthalate,DEHP]诱导的先天性尿道下裂大鼠模型上,研究细胞外信号调控激酶(extracellular signal-regulated kinase,ERK)1/2在DEHP暴露后的胎鼠阴茎中的表达变化,探讨尿道下裂发生机制。方法将SD孕鼠完全随机分为DEHP组[750 mg/(kg·d)DEHP+1.5 mL大豆油]和对照组(1.5 mL大豆油),每组20只,2组分别于母鼠怀孕天数(GD)第12～19天持续经口灌注给药。2组分别取10只孕鼠让其正常分娩,并计数每窝产雄性活仔鼠数量;出生后1、3、7、14、21、30日龄时称取雄性仔鼠体质量并测量肛门生殖器距离(anogenital distance,AGD);30日龄时逐个检查尿道下裂的发生情况。余孕鼠在GD20行剖宫产取雄性胎鼠,应用实时定量聚合酶链反应(qPCR)和免疫组化方法分别检测胎鼠阴茎组织中ERK1/2 mRNA和蛋白表达水平。结果 DEHP组孕期暴露诱导的尿道下裂发生率为28.2%。DEHP组每窝产雄性活仔鼠数量、各日龄雄性仔鼠体质量及AGD较对照组明显减少或缩短(P<0.01)。与对照组比较,DEHP组胎鼠阴茎组织中ERK1和ERK2 mRNA表达水平明显增加(P<0.05);DEHP组ERK1/2磷酸化蛋白表达水平有增加趋势。结论 DEHP诱导先天性尿道下裂发生可能与胎鼠阴茎组织中ERK信号的过度表达有关。
Objective To investigate the expression of extracellular signal-regulated kinase 1/2（ERK1/2） in the hypospadiac penis of fetal rats induced by maternal exposure to di-（2-ethylhexyl） phthalate（DEHP） in order to explore the etiology of hypospadias.Methods Forty timed-pregnant rats were randomly divided into 2 groups,control and DEHP induction group.The rats of the former group were given soybean oil,while those of later group were given gastric intubation of 750 mg/kg DEHP dissolved in soybean oil from gestation day（GD） 12 to 19.In each group,half of them（10 rats） were raised to deliver naturally,and live male pups were counted.The male pups＇ weight and their anogenital distance（AGD） were measured on postnatal day（PND） 1,3,7,14,21 and 30,and the hypospadias was observed on PND 30.The left（10 rats） were caesarean delivered at GD 20,and fetal rats penis were collected for real-time quantitative polymerase chain reaction（qPCR） and immunochemical assay to determine the mRNA expression and protein phosphorylation level of ERK1/2.Results The hypospadias incidence of DEHP group was 28.2%.Compared with normal control group,the decreased numbers of live male pups,body weight and AGD on PND 1,3,7,14,21 and 30 were observed.The mRNA expression of ERK1 and ERK2 in the fetal rat penis of DEHP group was increased significantly（P0.05）.And the protein phosphorylation levels of ERK1/2 in DEHP group also showed an increasing trend.Conclusion DEHP-induced hypospadias might be due to the over-expression of ERK1/2 in the fetal rat penis.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2013年第18期1932-1935,共4页
Journal of Third Military Medical University
基金
国家自然科学基金(81070475
81100415)
重庆市自然科学基金(CSTC2010BB5377)~~
