目的研究邻苯二甲酸二丁酯(DBP)在大鼠孕晚期染毒诱导子代雄性大鼠发生肛门直肠畸形(ARMs),并探讨DBP对子代雄性大鼠生长发育的影响。方法孕鼠20只,随机分为两组,怀孕第12~18天,每天分别予大豆油及DBP850mg/kg灌胃。出生后(PND)1d统计肛门闭锁发生率,测量雄性仔鼠体重和肛门生殖器距离(AGD)。PND7d观察肛门闭锁雄性仔鼠末端直肠及肛周组织的病理学改变。PND35d统计雄性仔鼠体重、体长(除尾)和腹围,解剖后对实质脏器(脑、心、肝、脾、肺、肾)以及生殖器官(睾丸、附睾)称重,计算脏器系数,评估发育情况。结果雄性仔鼠肛门闭锁发生率为39.5%。PND1d肛门闭锁雄性仔鼠体重及AGD分别为(4.876±0.067)g、(2.401±0.341)mm,对照组分别为(6.365±0.085)g、(2.993±0.403)mm,与对照组相比明显降低,差异有统计学意义(P〈0.05)。PND7d末端直肠及肛周组织病理显示典型的ARMs。PND35d肛门闭锁雄性仔鼠腹围及体长分别为(20.021±0.416)mm、(12.925±0.158)mm,对照组分别为(11.993±0.339)g、(14.943±0.171)mm,与对照组相比,腹围增加且体长缩短,差异有统计学意义(P〈0.05)。解剖后发现,肛门闭锁雄性仔鼠均发生巨结肠改变,实质脏器(脑、心、肝、脾、肺、左肾、右肾)以及生殖器官(左睾丸、右睾丸、左附睾、右附睾)脏器系数分别为(9.312±0.233)mg/g、(3.541±0.079)mg/g、(46.382±1.309)mg/g、(3.653±0.098)mg/g、(8.872±0.323)mg/g、(5.261±0.108)mg/g、(5.093±0.096)mg/g、(1.725±0.049)mg/g、(1.513±0.041)mg/g、(0.169±0.009)mg/g、(0.182±0.008)mg/g,对照组分别为(12.452±0.213)mg/g、(4.582±0.128)mg/g、(52.853±1.256)mg/g、(4.012±0.145)
Objective To induce anorectal malformations (ARMs) in male rats by maternal ex- posure to di-n-butyl phthalate (DBP) during late pregnancy and examine the development abnormali- ties in male rats. Methods Twenty pregnant rats were randomly divided into 2 groups. DBP was ad- ministered by gastric intubation at a dose of 850 mg/kg/d from gestation day (GD) 12 to 18. At post- natal day (PND) 1, body weight was measured and the incidence of ARMs and anogenital distance (AGD) were evaluated. At PND7, histological changes of ARMs were observed. At PND35, body weight, abdominal circumference and body length (with tail removal) were observed. The develop- mental abnormalities were also examined by evaluating the values of organ to body weight ratios of sol id organs (brain, heart, liver, spleen, lung & kidney) and reproductive organs (testes & epididy mis). Results The incidence of ARMs was 39. 5%. Body weigh and AGD of ARMs at PND1 were(4. 876 ± 0. 067) g, (2. 4111 ± 0. 341 ) mm versus (6. 365 ± 0. 085) g, (2. 993 ± (1. 4113) mm in controls. The difference had statistical significance (P〈0. 05). At PND7, histological analysis was conducted for con? rming the malformations. The abdominal circumference of ARMs signi? cantly increased at PND35 whereas body length (with tail removal) of ARMs were (20. 021 ± 0. 416), (12. 925 ± 1). 158) mm versus (11. 993 ± 0. 339), ( 14. 943 ± 0. 171 )mm in controls. The differences had statistical sig- nificance (P〈0. 05). Autopsy analysis of ARMs suggested secondary megacolon. The organ to body weight ratios of solid organs (brain, heart, liver, spleen, lung, left kidney & right kidney) and repro- ductive organs (left testicle, right testicle, left epididymis & right epididymis) were (9. 312± 0. 233), (3. 541 ±0. 079), (46. 382 ± 1.31)9), (3. 653 ± 0. I)98), (8. 872 ± 0. 323), (5. 261 ± 0. 11)8), (5. 1193 ± (1. 1196), (1. 725 ± 0. 04