维甲酸改变腭突发育关键时期细胞增殖和凋亡导致腭裂  

Induced cleft palat by Retinoic acid through altering the cell proliferation and apoptosis at the key stages of palatal development

作　　者：胡晓 李叶扬 梁岷 林伟华 

机构地区：[1]暨南大学医学院附属广州市红十字会医院烧伤整形科,510220

出　　处：《中华整形外科杂志》2016年第3期220-224,共5页Chinese Journal of Plastic Surgery

基　　金：国家自然科学基金（81501689）;广东省自然科学基金（2014A030310423）;广州市医药卫生科技项目（20151A011018）

摘　　要：目的探讨维甲酸对腭发育关键时期腭突间充质细胞和上皮细胞增殖和凋亡的影响，确定其致腭裂的胚胎学作用节点。方法将100只怀孕12d（E12）的C57孕母鼠采用随机数字表法平均分为2组，实验组灌胃维甲酸1次，70mg／kg，对照组灌胃玉米油，分别取E13．5、E14．5、E15．5和E17．5的胎鼠头部制成石蜡切片，HE染色观察腭突的形态，BrdU和TUNEL染色分别检测间充质和上皮细胞增殖、凋亡情况。结果在E13．5～15．5切片中，维甲酸处理组的前部腭突间充质细胞增殖明显增多，差异有统计学意义。后部腭突间充质细胞的增殖无明显差异。对照组前部和后部的上皮细胞增殖均无明显差异。E13．5～14．5切片中维甲酸处理组口腔侧上皮细胞的凋亡减少。结论维甲酸诱导腭突间充质细胞过度增殖，口腔面上皮细胞凋亡减少，腭突不能正常抬升和融合，最终导致腭裂发生。Objective To investigate the effects of retinoic acid （RA） on the proliferation and apoptosis of mesenchyme and epithelium at the key stages of palatal development, and to determine the embryonic alterations associated with cleft palate. Methods 100 pregnant C57 females （E12） were equally divided into two groups. The experimental group was administered RA once （70 mg/kg） while the control group was administered corn oil only, and the heads of the embryos at E13.5 - 17.5 were collected and processed to paraffin. Sections were stained with hematoxylin and eosin for the morphological assessment of anterior, posterior, left and right palate, and BrdU and TUNEL assays for the detection of proliferation and survival of palatal mesenchyme and epithelium. Results Simple treatment of RA at 70 mg/kg caused an incidence of 100% cleft palate. During E13.5 - 15.5, cell proliferation was significantly promoted on the anterior palatal mesenchyme in the RA group, while no difference for the posterior palatal mesenchyme. Besides, the cell proliferation on anterior and posterior epithelium was comparable between the control and RA group. Less apoptotic cells were observed on epithelium during E13.5- 14.5 in the RA group. Conclusions RA induces excessive cell proliferation of palatal mesenchyme, causing abnormal vertical palatal growth and failure of palatal shelves contact and fusion, which finally lead to cleft palate. RA also increases epithelium apoptosis.

关 键 词：腭裂 维甲酸 细胞增殖 细胞凋亡 

分 类 号：R782.22[医药卫生—口腔医学]