维甲酸诱导大鼠产生肛门直肠畸形及其伴发畸形  

Anorectal malformation and accompanied malformations in rat fetuses induced by retinoic acid

作　　者：郭俊斌[1] 王练英[1] 张志波[1] 白玉作[1] 

机构地区：[1]中国医科大学附属第二医院小儿外科,沈阳110004

出　　处：《中国优生与遗传杂志》2005年第1期93-95,共3页Chinese Journal of Birth Health & Heredity

基　　金：国家自然科学基金资助项目 (批准号 :3 0 3 0 0 3 70 )

摘　　要：目的　利用维甲酸诱导大鼠肛门直肠畸形并探讨维生素A类物与肛门直肠畸形发生之间的关系。方法　利用成熟未孕的Wistar大鼠 ,在妊娠 10d时经胃管注入维甲酸 ,诱导产生肛门直肠畸形动物模型 ,分别在妊娠 16、18、2 0d时剖宫取出胎鼠 ,进行实体观察、畸形率统计 ,同时行病理形态学研究。对照组仅给予橄榄油 ,剖宫时间及观察项目同致畸组。结果　维甲酸致畸组共获得胎鼠 96只 ,其中肛门直肠畸形发生率 81.3% (78/ 96 ) ,显性脊柱裂 4 6 .9% (45 / 96 ) ,无尾畸形 70 .8%(6 8/ 96 ) ,足畸形 37.5 % (36 / 96 )。对照组剖出 74只胎鼠 ,均未见上述畸形。致畸组与对照组在妊娠 16d、18d、2 0d时身长及体重相应各组数据经t检验统计差异显著 (P <0 .0 1) ,致畸组均较对照组为差。结论　维甲酸是一种良好的诱导肛门直肠畸形动物模型的致畸剂 ,其发生机制可能是过量维甲酸通过干扰维生素A酸信号系统影响正常胚胎发生所致。Objective: To explore the relative of the pathogenesis of anorectal malformation and retinoids. Methods:Timed-pregnant rats were gavage-fed 135mg/kg of all-trans retinoic acid on the tenth gestational day (E10).Fetuses were obtained on E16, E18 and E20 and examined macroscopically and microscopically. A control group received olive oil only and fetuses were obtained at the same time and examined. Results: 96 fetuses were obtained from the treated rats. Among the 96 fetuses 81.3%(78/96)had anorectal malformation , 46.9%(45/96)had spina bifida, 70.8%(68/96)had no tail and 10 had circular tail or shorter tail,37.5%(36/96)had foot malformation and 10.4%(10/96)were dead fetuses and 8.3%(8/96) were normal in appearance. In the control group 74 fetuses were obtained and they were normal in appearance. The total body lengthes(TBL) and body weights(BW) on E16 ,E18 and E20 of the treated fetuses were compared with the data of the control group. There were significant difference between the treated group and the control group (P<0.01) and the treated group were poorer than the control group.Conclusions: ATRA is an excellent teratogen used to induce the animal model of anorectal malformations. The results suggest overdose of all-trans retinoic acid affected the distal embryo development especially in the hind-gut region through disturbing the retinoid-mediated signal transduction.

关 键 词：维甲酸 动物模型 肛门直肠畸形 大鼠 

分 类 号：R726.5[医药卫生—儿科]