全反式维甲酸对小鼠颅颌面部发育影响的研究

The influence of all-trans retinoic acid on the craniomaxillofacial development of mice

目的:探讨妊娠期全反式维甲酸(atRA)摄入对胎鼠颅颌面部发育的影响。方法:C57BL孕鼠随机分成4组(n=5)妊娠第10天,实验组分别给予60、80、100 mg/kg atRA)灌胃1次,对照组给予相同剂量的玉米油灌胃。第19天取胚胎,记录基本情况取胎鼠头作头颅软组织侧貌分析拍摄X线片作颅颌面部骨骼测量。结果:RA≥80 mg/kg的2个实验组胎鼠体重减轻、体长缩短,出现明显颅颌面部畸形,畸胎率随RA剂量增高而升高。100 mg/kg组胎鼠下颌体(BD)缩短,上颌骨(∠NAK)、下颌骨(∠NBD)后缩(P<0.01);∠SNG则大于对照组(P<0.01)。X线头影测量发现:维甲酸各剂量组胎鼠颅颌面部矢状向缩短(Op-Rh)(P<0.01);维甲酸≥80 mg/kg的2个实验组胎鼠的颅穹窿长度(Pa-Na)和高度(Fp-Os)均小于对照组(P<0.05,P<0.01)。结论:维甲酸剂量依赖性抑制颅颌面部骨骼发育。

Objective：To study the influence of all-trans retinoic acid（atRA） on craniomaxillofacial development of C57 mice.Methods：Pregnant C57 BL mice were divided into 4 groups（n = 5） at gestation day（GD） 10.Mice in three atRA-induction groups were given atRA of 60,80 and 100 mg/kg,respectively.The mice in control group were given the equivalent volume of corn oil.All pregnant mice were sacrificed at GD19 and the embryos were collected.Stereo microscope was used to observe the craniomaxillofacial morphology.Standardized radiographs were taken and cephalometric analysis was performed.Results：The embryonic body length and body mass of control group surpassed those of 80 and 100 mg/kg atRA groups（P〈0.05,P〈0.01）.atRA induced craniomaxillofacial malformations and maldevelopment.The mice induced by atRA exhibited a shorter mandibular body and more retrusive position of maxillary and mandibular（∠NAK and ∠NBD） when compared with their norm（P〈0.01）.Significant decrease in craniofacial length（Op-Rh） was observed in all atRA-induced groups（P〈0.01）.Decreases in cranial vault height（Fp-Os） and cranial vault length（PaNa） dimensions were observed in 80 and 100 mg/kg atRA groups（P〈0.05,P〈0.01）.Conclusion：Exogenous atRA dose-dependently induces retardation of craniomaxillofacial morphology in embryo of C57 BL mice by inhibition of the sagital and vertical dimension development of the bone.