甲酰四氢叶酸拮抗维甲酸诱导颅面部畸形的体外研究

Prevention of retinoic acid-Induced craniofacial anomalies by folinic acid in vitro study

目的探讨甲酰四氢叶酸(FA)对维甲酸(RA)诱导颅面部畸形的作用。方法采用植入后全胚胎培养模型,将8．5日龄的ICR小鼠胚胎在大鼠即刻离心血清中旋转培养48 H,分别设立空白对照组体积分数为0．1％二甲基亚砜、4×10-7 MOL／L RA、4×10-7 MOL／L RA+10-3 MOL／L FA、4×10-7 MOL／L RA+10-4 MOL／L FA、4×10-7 MOL／L RA+10-5 MOL／L FA共5个剂量组。观察各组胚胎的生长发育和组织器官形态分化。结果4×10-7 MOL／L RA对胚胎的脑部、听觉系统、腮弓、下颌突、腮弓长发育有致畸作用,与对照组相比较,差异有显著性(P<0．05)。当补充 10-3 MOL／L和10-4 MOL／L的FA叶酸对胚胎脑部、听觉系统、腮弓、下颌突、鳃弓长发育的致畸作用有明显拮抗作用,差异有显著性(P<0．05);10-5 MOL／L FA的拮抗作用不明显,与4×10-7 MOL／L RA组比较,差异无显著性(P>0．05)。结论FA能明显抑制RA诱导的小鼠早期颅面部畸形。

Objective Craniofacial anomalies is one of the most common human congenital birth defects. Previous studies have shown that in ntero exposure of the mouse embryo to high doses of alltrans-retinoic acid （at RA） produces malformations of craniofacial region. Effects of folinic acid on retinoic acid-induced craniofacial anomalies were investigated in mouse embryos. Methods Whole embryo culture system was used in this research. Embryos were exposed to control, 4× 10^-7 mol/L RA, 4× 10^-7 mol/L RA＋10^-3 mol/L FA, 4×10^-7 mol/L RA＋10^-4 mol/L FA, and 4× 10^-7 mol/L RA＋I OS mol/L FA, respectively, and scored for growth and development at the end of the 48th culture period. Results Development of brain, otic system, branchial arch, mandible, length of branchial arch decreased at the concentration of 4 ×10^-7 mol/L RA; however, development of the above indexes at the high concentrations of folinic acid （≥10^-4 mol/ L） were improved compared to at the concentration of 4×10^-7 mol/L RA （P 〈 0.05）. Conclusion folinic acid can prevent retinoic acid-induced mouse early craniofacial anomalies.