塑化剂邻苯二甲酸二乙基己酯诱导大鼠尿道下-第三军医大学学报.DOC

PAGE PAGE 1 塑化剂邻苯二甲酸二(2-乙基)己酯诱导大鼠尿道下裂的实验研究 李明勇1；华焱1；陈柏林1；邱林2；何昀1；温晟1；龙春兰1；魏光辉1 [重庆医科大学附属儿童医院泌尿外科1，烧伤整形外科2；儿童发育疾病研究省部共建教育部重点实验室，儿科学重庆市重点实验室，重庆市（儿童发育重大疾病诊治与预防）国际科技合作基地，重庆400014] [摘要] 目的 采用塑化剂邻苯二甲酸二(2-乙基)己酯（DEHP）诱导建立大鼠尿道下裂动物模型，初步观察DEHP的外生殖器毒性作用。方法 孕鼠40只，随机分成4组：大豆油对照组和DEHP低中高三个剂量组（分别为500,750,1000mg/kg bw/day）。在怀孕天数（GD）第12-19连续灌胃，出生后（PND）第1天即对新生鼠进行计数，测量肛门生殖器距离（AGD）和称量体重；PND30测量阴茎长度，观察每组雄性仔鼠的尿道开口位置，判断有无尿道下裂及其严重程度并切取整个阴茎进行病理组织苏木精-伊红（HE）染色。结果 与对照组相比，随着DEHP剂量增大，仔鼠的体重减轻、AGD和阴茎长度缩短明显；同时，每窝总产仔数及雄性仔鼠数也均较对照组有显著减少（P0.05）。DEHP低中高剂量组均诱导出雄性仔鼠尿道下裂畸形，其发生率分别为10.7%，30.6%和37.0%，组织横截面石蜡切片HE染色予以验证。结论 DEHP对大鼠亲代和子代均有一定的生殖毒性，尤其对子代的外生殖器毒性作用显著。DEHP的生殖毒性与尿道下裂畸形的发生相关。 [关键词] 尿道下裂；邻苯二甲酸二(2-乙基)己酯；塑化剂；SD大鼠；动物模型 [中图法分类号] R726.9；R124.3 [文献标志码] A Study on hypospadiac male rats induced by maternal exposure to di-(2-Ethylhexyl) phthalate plasticizer Li Mingyong1, Hua Yi1, Chen Bolin1, Qiu Lin2, He Yun1, Wen Sheng1, Long Chunlan1, Wei Guanghui1 Department of Pediatric Urology Surgery1, Department of Pediatric Burns and Plastic Surgery2; Chongqing Medical University affiliated Childrens Hospital, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China. Corresponding author: Wei Guanghui, Tel. : 023 E-mail: HYPERLINK mailto:ghwei@ ghwei@. [Abstract] Objective The aim of this study was to establish a hypospadiac rat model by maternal exposure to di-(2-Ethylhexyl) phthalate (DEHP) plasticizer and to evaluate the developmental abnormalities of hypospadiac male rats. Methods Timed-pregnant rats were given DEHP by gastric intubation at doses of 0, 500,750 or 1000 mg/kg body weight (bw)/day from gestation day (GD) 12 to 19 to establish a hypospadiac rat model. On postnatal day (PND) 1, Live pups were counted, male pups were weighed and their anogenital distance were measured. The hypos