Smad2/3信号分子在小鼠胚胎腭发育和腭裂形成中的表达

背景：部分学者通过体外器官培养研究认为全反式维甲酸干扰了Smad2/3在腭部的表达,具体机制尚不明确。目的：观察腭突Smad2/3信号分子在胚鼠腭部发育及腭裂形成过程中的表达变化。方法：54只C57BL/6J近交系孕鼠随机分为3组,在妊娠10d,实验组一次性灌胃全反式维甲酸100mg/kg诱导胚鼠两侧腭突不能在中线融合,建立腭裂畸形动物模型;植物油对照组灌胃10mL/kg橄榄油,空白对照组不做处理。结果与结论：在植物油对照组中,从妊娠13d18时到妊娠14d18时腭间充质细胞中Smad2/3免疫阳性表达逐步增高,至妊娠15d8时表达开始出现下降,实验组也表现为这一变化趋势,且同一组间表达较植物油对照组明显;在腭中嵴上皮细胞中,植物油对照组随着腭突的融合,腭中嵴上皮带消失,Smad2/3表达也明显下降,实验组始终未融合,未见明显的Smad2/3阳性细胞。在整个胚腭正常发育和腭裂形成过程中,空白对照组与植物油对照组Smad2/3阳性细胞表达几乎无差异。提示过量全反式维甲酸可能通过干扰腭中嵴上皮细胞及间充质细胞中Smad2/3信号分子的表达,从而影响小鼠胚腭上皮间充质转化,与腭裂形成密切相关。

Expression of Smad2/3 in normal palate development and cleft palate formation during mouse embryogenesis

BACKGROUND：Through in vitro organ culture studies,a few scholars consider that all-trans retinoic acid（at RA） can interfere with palatal expression,but the underlying mechanisms remain unclear.OBJECTIVE：To investigate the expression changes of Smad2/3 of palatal shelves in normal palatal development and cleft palate formation during mouse embryogenesis.METHODS：Both sides of the embryonic mouse palatal shelves were induced by excess at RA so that they could not integrate at the midline.Then,a mouse model of cleft palate was established,and 54 C57BL/6J inbred pregnant mice were randomly divided into experimental group,vegetable oil control group and blank control group.At GD 10,the mice in the experimental group were subjected to once gastric perfusion with 100 mg/kg at RA,and those in the vegetable oil control group underwent lavage with 10mL/kg olive oil,while those in the blank control group had no treatment.RESULTS AND CONCLUSION：Smad2/3 positive expression was increased gradually in the embryonic palatal mesenchymal cells from GD1318 to GD148,but few positive cells were observed after GD158,while this trend was also found in the experimental group.In addition,Smad2/3 positive expression at the same developmental time was more obvious than that of the vegetable oil control group.In palatal medial edge epithelium,with the integration of bilateral palatal shelves,the ridge in palate belt disappeared,and Smad2/3 expression was decreased significantly.In the experimental group,the integration did not appeared,besides,significant Smad2/3 positive cells were not found.There was no significant difference in Smad2/3 positive cell expression between the blank control and vegetable oil groups in normal palatal development and cleft palate formation during mouse embryogenesis.These results suggest that excess at RA can interfere with Smad2/3 expression in the embryonic palatal medial edge epithelium and embryonic palatal mesenchymal cells,and thereby influence epithelial-mesenchymal transformation in mice,which is closely related to the formation of cleft palate.