中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 502-507.doi: 10.4103/1673-5374.179070

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊柱裂大鼠羊水microRNA表达谱分析可为脊柱裂早期干预提供新靶标？

  

  • 收稿日期:2015-08-15 出版日期:2016-03-15 发布日期:2016-03-15

Altered microRNA expression profiles in a rat model of spina bifida

Pan Qin 1, Lin Li 2,, Da Zhang 1, Qiu-liang Liu 1, Xin-rang Chen 1, He-ying Yang 1, Ying-zhong Fan 1, Jia-xiang Wang 1   

  1. 1 Department of Pediatric Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
    2 Department of Dermatology, Zhengzhou Children’s Hospital, Zhengzhou, Henan Province, China
  • Received:2015-08-15 Online:2016-03-15 Published:2016-03-15
  • Contact: Jia-xiang Wang, Ph.D.,jiaxiangw@sohu.com.

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摘要：

miRNAs动态调节神经发育，但以往对脊柱裂小鼠发病和治疗机制的研究中，极少涉及miRNA的研究。实验将E10孕鼠灌胃全反式维甲酸诱导建立脊柱裂胚鼠模型，以灌胃橄榄油为对照，使用miRNA芯片进行分析E20大鼠羊水中miRNA表达谱，发现与孕正常胚胎的大鼠母体相比，脊柱裂胚胎大鼠母体羊水中的11种miRNA表达出现了改变，其中miRNA-9，miRNA-124a和miRNA-138三种表达下降超过2倍，miRNA-134表达上升超过4倍。实时定量反转录PCR证实上述结果。基因芯片数据的聚类分析表明，这些miRNA的表达可以区分脊柱裂与正常大鼠。随后的生物信息学分析也提示上述改变的miRNA涉及了多种细胞学通路，其中就包括了神经系统发育信号通路。该组实验证实了miRNA通过调控多个细胞功能学通路参与脊柱裂的发病过程，为脊柱裂的早期诊断和治疗提供了新的干预靶向目标。

关键词: 神经再生, 脊柱裂, 羊水, microRNA, 全反式维甲酸, 芯片分析, 反转录PCR, MAPK

Abstract:

MicroRNAs (miRNAs) are dynamically regulated during neurodevelopment, yet few reports have examined their role in spina bifida. In this study, we used an established fetal rat model of spina bifida induced by intragastrically administering olive oil-containing all-trans retinoic acid to dams on day 10 of pregnancy. Dams that received intragastric administration of all-trans retinoic acid-free olive oil served as controls. The miRNA expression profile in the amniotic fluid of rats at 20 days of pregnancy was analyzed using an miRNA microarray assay. Compared with that in control fetuses, the expression of miRNA-9, miRNA-124a, and miRNA-138 was significantly decreased (> 2-fold), whereas the expression of miRNA-134 was significantly increased (> 4-fold) in the amniotic fluid of rats with fetuses modeling spina bifida. These results were validated using real-time quantitative reverse-transcription polymerase chain reaction. Hierarchical clustering analysis of the microarray data showed that these differentially expressed miRNAs could distinguish fetuses modeling spina bifida from control fetuses. Our bioinformatics analysis suggested that these differentially expressed miRNAs were associated with many cytological pathways, including a nervous system development signaling pathway. These findings indicate that further studies are warranted examining the role of miRNAs through their regulation of a variety of cell functional pathways in the pathogenesis of spina bifida. Such studies may provide novel targets for the early diagnosis and treatment of spina bifida.

Key words: nerve regeneration, spina bifida, amniotic fluid, all-trans retinoic acid, microarray, microRNA, reverse transcription-polymerase chain reaction, MAPK, neural regeneration