膜联蛋白A4在肛门直肠畸形和先天性脊柱裂大鼠脊髓中的异常表达.docVIP

  膜联蛋白 A4 在肛门直肠畸形和先天性脊柱 裂大鼠脊髓中的异常表达# 5 10 15 20 25 30  摘要：目的：对反式维甲酸致先天性肛门直肠畸形及脊柱裂大鼠两种畸形动物的脊髓组织中 共同的差异表达蛋白进行蛋白质组学研究。方法：应用 2D 双向电泳为基础的蛋白质组学对 反式维甲酸致先天性肛门直肠畸形及脊柱裂大鼠两种畸形动物的脊髓组织进行研究。后续采 用免疫印迹和实时定量 PCR 分析方法对双向电泳筛选出的异常表达蛋白进行验证。结果： 蛋白质组学研究发现膜联蛋白 A4 在先天性肛门直肠畸形及脊柱裂大鼠脊髓组织中表达均异 常降低，且减低程度与畸形严重程度相关。免疫印迹和实时定量 PCR 分析进一步验证了双 向电泳的结果。结论：反式维甲酸致先天性脊柱裂大鼠脊髓组织中，膜联蛋白 A4 于蛋白水 平和基因水平的表达均异常降低，提示两种畸形可能具有相同神经损伤模式。 关键词：小儿外科；肛门直肠畸形；显性脊柱裂，膜联蛋白。 中图分类号： R726.5 Alteration of Annexin A4 in rat fetuses with anorectal malformation and spina bifida aperta FAN Yang, MIAO Jianing, YUAN Zhengwei (Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang,110004, P.R. China) Abstract: Objective:To study the different expression proteins in fetal spinal cord with all-trans retinoic acid induced anorectal malformation and spina bifida rats by 2D-electrophoresis based proteomics. Methods: We studied the differently expressed proteins in fetal spinal cords of rats with anorectal malformation and spina bifida by 2D-electrophoresis based proteomics.Then Western blot analysis and real-time PCR were performed to verified the results of 2D-electrophoresis. Result: Annexin A4 was down-regulated in spinal cord of fetal rats with anorectal malformation and spina bifida by proteomics study, and the level of altered annexin A4 was related with the severity of malformation. This result was verified by western blot and real-time PCR analysis. Conclusions: In fetal spinal cord with all-trans retinoic acid induced anorectal malformation and spina bifida rats, annexin A4 expression decressed in both protein and genetic level, which might reflect the common neural injury in the two type of malformation. Key words: pediatric surgery;anorectal malformation;spina bifida aperta;annexin. 35 先天性肛门直肠畸形和先天性脊柱裂均为常见的小儿先天性畸形，为多基因遗传病,是 遗传因素和环境因素共同作用的结果。这些畸形具体发病机制不清,病理改变复杂,预防和治 疗尚无良策。我们的既往研究发现先天性肛门直肠畸形中大多数存在明显的腰骶部脊髓神经 发育异常[1]。利用药物致畸制作动物模型过程中我们发现维甲酸致畸动物可同时产生先天性 40 肛门直肠畸形、先天性脊柱