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 (8): 1285-1292.doi: 10.4103/1673-5374.189194

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

microRNA-27a保护氧糖剥夺诱导海马神经元损伤的机制

  

  • 出版日期:2016-08-31 发布日期:2016-08-31
  • 基金资助:
    国家自然科学基金(81101159)

Protective mechanisms of microRNA-27a against oxygen-glucose deprivation-induced injuries in hippocampal neurons

Qun Cai1, Ting Wang2, Wen-jie Yang3, Xing Fen1, *   

  1. 1 Department of Neonatology, Children’s Hospital of Soochow University, Suzhou, Jiangsu Province, China 2 Department of Emergency, Affliated Hospital of Nantong University, Nantong, Jiangsu Province, China 3 Medical College of Nantong University, Nantong, Jiangsu Province, China
  • Online:2016-08-31 Published:2016-08-31
  • Contact: Xing Fen, M.D., fenxing@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81101159; and the Natural Science Foundation of Jiangsu Province of China, No. BK20151268.

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摘要：

已有研究报道，在胎儿宫内窘迫引起的缺氧损伤中，大脑皮质神经元miR-27a的表达下调，可促进神经元的凋亡。作者假设microRNA-27a可通过抑制调控氧化应激反应的一个重要转录因子FOXO1保护氧糖剥夺诱导的海马神经元损伤。故实验中将miR-27a mimic转染至大鼠海马神经元氧糖剥夺模型中，使之过表达miR-27a后发现，海马神经元的细胞活力增强，凋亡相关蛋白Caspase 3的表达下调。荧光素酶报告基因系统检测发现，miR-27a在海马神经元中可直接与FOXO1 3’UTR接合，抑制FOXO1基因表达，说明FOXO1基因为miR-27a的靶基因。结果证实，microRNA-27a保护氧糖剥夺诱导的海马神经元损伤，其机制与其靶向FOXO1，并抑制Caspase 3蛋白表达有关。 

orcid:0000-0002-4540-1348 (Qun Cai)

关键词: 神经再生, 脑损伤, miR-27a, 缺氧缺血, 海马神经元, 氧糖剥夺, 细胞存活, 凋亡, Caspase 3, FOXO1, 荧光素酶报告基因系统, 神经保护

Abstract:

Hypoxic injuries during fetal distress have been shown to cause reduced expression of microRNA-27a (miR-27a), which regulates sensitivity of cortical neurons to apoptosis. We hypothesized that miR-27a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1, an important transcription factor for regulating the oxidative stress response. miR-27a mimic was transfected into hippocampal neurons to overexpress miR-27a. Results showed increased hippocampal neuronal viability and decreased caspase-3 expression. The luciferase reporter gene system demonstrated that miR-27a directly binded to FOXO1 3′UTR in hippocampal neurons and inhibited FOXO1 expression, suggesting that FOXO1 was the target gene for miR-27a. These fndings confrm that miR-27a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries. The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.

Key words: nerve regeneration, brain injury, miR-27a, hypoxic-ischemic, hippocampal neurons, oxygen-glucose deprivation, cell survival, apoptosis; caspase 3, FOXO1, luciferase reporter gene system, neuroprotection, neural regeneration