维甲酸诱导显性脊柱裂胎鼠骶尾部神经前体细胞凋亡的变化规律研究
袁正伟
基金项目：高等学校博士学科点专项科研基金（博导类）（20122104110010）
作者简介：袁正伟（1964-），男，教授，主要研究方向：常见小儿先天畸形胚胎发生机制与早期诊断、治疗.

（中国医科大学附属盛京医院卫生部小儿先天畸形重点实验室）
摘要：神经管畸形（Neural tube defects, NTDs）是最常见的严重中枢神经系统先天畸形，世界范围内人群发生率为0.6‰~6‰，但目前尚无良好治疗方法。我们前期的研究表明神经元在NTDs 大鼠胚胎期的发育异常，然而神经元发育损伤的机制尚不明确。本研究利用全反式维甲酸诱导的显性性脊柱裂大鼠模型，在NTDs 发生早期（胚胎发育的第11、12、13 天），利用免疫荧光染色检测脊髓缺损部位细胞凋亡的变化。结果显示NTDs 大鼠胚胎骶尾部神经管中神经前体细胞凋亡增多，这可能是脊柱裂胚胎神经元发育异常的主要原因之一。
关键词：医学遗传学；神经管畸形；细胞凋亡。
中图分类号：R394.1
 Altered apoptosis in developing neuroepithelium of lumbo-sacral neural tubes in spina bifida aperta in rat
YUAN Zhengwei
(Key Laboratory of the Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004)
Abstract: Neural tube defects (NTDs) are severe congenital anomalies of the central nervous system that result from incomplete neurulation, the frequency of NYDs in human is 0.6‰~6‰, but most of the patients who survive with NTDs still suffer from associated conditions.Our previous work has demonstrated that motor and sensory neurons develop defectively in rat embryos with spina bifida aperta. In this paper, we investigated cell apoptosis and proliferation of neural progenitor cells in the spinal neural tube during neurulation in retinoic acid (atRA)-induced spina bifida in fetal rats. Cell apoptosis was assessed by TUNEL assay on serially sectioned samples of rat embryos with spina bifida. We found an excess of apoptosis in the neuroepithelium of embryos with spina bifida, which became more marked as embryos progress from E11 to E13. Thus, atRA-induced spina bifida in rat shows perturbed apoptosis of neural progenitors in the lumbo-sacral spinal cord during embryonic development, which might be attributed to the developmental deficit of neurons.
Key words: Medical genetics; Neural tube defects; cell apoptosis.