腭发育不同时期维甲酸对腭突细胞增殖和凋亡的影响

目的研究维甲酸对小鼠腭突融合期细胞增殖和细胞凋亡的影响。方法在SPF级C57BL/6J近交系母鼠妊娠10 d和12 d给予维甲酸（RA）建立小鼠腭裂模型，利用BrdU免疫组化方法和脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）检测胚胎15 d（即腭突融合期）小鼠腭突中细胞增殖及细胞凋亡的表达和分布。结果10 d给药组腭胚间充质细胞及腭中嵴上皮细胞中BrdU阳性细胞率和TUNEL阳性细胞率均低于对照组，12 d给药组和对照组BrdU阳性细胞率和TUNEL阳性细胞差异无统计学意义。结论维甲酸作用于腭发育的不同时期对腭突细胞增殖及凋亡水平有不同的影响，作用于腭突发生前期可引起腭间充质细胞增殖抑制、凋亡过度而发生腭裂，作用于腭突快速生长期可能影响腭中嵴上皮细胞的上皮间充质转化和迁移等其他转归形式。

Spatial and temporal changes of palatal cell proliferation and cell apoptosis of retinoic acid induced mouse cleft palate in different embryonic stages

Objective To study the effect of retinoic acid(RA) on cell proliferation and apoptosis of palatalshelves by 5-bromo-2-deoxyuridine(BrdU) and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL).Methods C57BL/6J mice were used to establish the RA induced cleft palate animal model, in which the pregnant mice were given a single dose of RA at 100 mg/kg body weight on gestation day 10(GD10) and GD12, re-spectively.Specimens were prepared for immunohistochemical staining by using BrdU and TUNEL monoclonal anti-bodies.Results The percentages of BrdU positive cells of embryonic palatal mesenchyme(EPM) and medial edge epi-thelium(MEE) in GD10 RA group were both obviously lower than that of control group.There was no differencebetween GD12 RA group and control group.Abnormally intense staining of TUNEL was detected in the palatal mesenchymal cells of GD10 day RA group but not in control group and GD12 day RA group.Conclusion After exposure of embryonic mice to RA on GD10, the proliferation and apoptosis of palatal mesenchymal cells are increased, this causes the smaller size of shelves and failure of fusion.The MEE cells keep a bilayer midline epithelial seam after exposure on GD12 with normal apoptosis, this indicates that cell apoptosis in MEE cells be not the only process required for palatal fusion.