维甲酸诱导小鼠腭裂发病机制的实验研究

目的 观察维甲酸（retinoic acid,RA)诱导胚鼠腭突发育的形态学变化，探讨胚鼠腭部转化生长因子（transforming growth factor,TGF)β1、TGFβ3、表皮生长因子（epidermal growth factor,EGF)及BCL2的表达在RA诱导腭裂发病机制中的意义。方法 采用显微镜观察胚腭的发育过程，原位杂交和免疫组化检测TGFβ1、TGFβ3、EGF及BCL2基因在胚腭中的表达。结果 RA引起双侧腭突的形成，使双侧腭突不能接触或接触后不能融合形成中嵴上皮带，以及可调控TGFβ1、TGFβ3、EGF及BCL2在鼠胚腭部的表达。结论 RA抑制中嵴上皮细胞（MEPM）增殖，引起双侧腭突的形成，诱导MEE细胞殿堂分化，使双侧腭突不能接触融合，而最终导致腭裂形成及TGFβ1、TGFβ3、EGF在鼠胚腭部表达的变化与RA诱导腭裂的形成密切相关。

Study on etiology of retinoic acid-induced cleft palate in mouse

OBJECTIVE: To investigate the morphologic changes of embryonic palatal development exposed to retinoic acid (RA) in mouse, and to detect the significance of the expression of TGFbeta1, TGFbeta3, EGF and BCL2. METHODS: The stage of palatal development was examined by light microscopy. S-P immunohistochemistry and in-situ hybridization was used to detect spatio-temporal patterns of expression of TGFbeta1, TGFbeta3, EGF and BCL2 in embryonic palate. RESULTS: The fetus exposed to RA resulted in formation of small palatal shelves without contact and fusion of each other to form and intact palate. RA can regulate the embryonic palatal expression of genes involved in RA-induced cleft palate. CONCLUSIONS: RA can inhibit the proliferation of MEPM cell to form small palatal shelves and induce abnormal differentiation of MEE cell causing the bi-palatal shelves no contact and fuse with each other, then induce the formation of cleft palate. RA can regulate the spatio-temporal patterns of expression of TGFbeta1, TGFbeta3 and EGF in embryonic palatal processes and the change of special expression of these genes in embryonic palatal processes are involved in RA-induced cleft palate.