中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (7): 749-756.doi: 10.4103/1673-5374.131581

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

调节细胞外信号转导激酶可减轻糖尿病脑缺血大鼠海马神经元的损伤

  

  • 收稿日期:2014-02-06 出版日期:2014-04-15 发布日期:2014-04-15

Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

Yaning Zhao 1, Jianmin Li 2, Qiqun Tang 1, Pan Zhang 1, Liwei Jing 1, Changxiang Chen 1, Shuxing Li 1   

  1. 1 College of Rehabilitation, Hebei United University, Tangshan, Hebei Province, China
    2 Affiliated Hospital of Hebei United University, Tangshan, Hebei Province, China
  • Received:2014-02-06 Online:2014-04-15 Published:2014-04-15
  • Contact: Yaning Zhao, College of Rehabilitation, Hebei United University, Tangshan 063000, Hebei Province, China, zyning789@126.com.
  • Supported by:

    This study was supported by the Hebei Province Natural Science Program, No. H2012401007; a grant from the foundation Key Project of Hebei Province Education Ministry, No. ZD2010106.

摘要:

脑缺血急性期脑组织细胞外信号调节激酶(ERK1/2)可出现激活现象。我们假设糖尿病脑缺血再灌注病理进程中ERK1/2活化可对神经元损伤起保护作用,实验对糖尿病脑缺血再灌注模型大鼠采用ERK1/2抑制剂U0126预处理,可见海马CA1区存活神经元数量减少,下调海马CA1区神经元中的磷酸化ERK1/2蛋白和细胞DNA修复相关的Ku70蛋白表达,并上调促凋亡基因Bax蛋白的表达。结果表明,抑制ERK1/2活性,可进一步加剧糖尿病脑缺血再灌注过程中大鼠海马神经元的丢失,进一步减弱海马神经元中DNA的修复能力,并加速海马神经元的凋亡。作者认为,ERK1/2激活可对糖尿病脑缺血再灌注海马神经元的损伤起保护作用。

关键词: 神经再生, 脑损伤, 脑缺血再灌注, DNA修复激酶, 细胞外信号转导激酶, 信号转导通路, Bax, 凋亡, 海马, 大鼠, 免疫组织化学, 蛋白印迹

Abstract:

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

Key words: nerve regeneration, brain injury, cerebral ischemia/reperfusion, DNA dependent protein kinase, extracellular signal-regulated kinase, Bax, apoptosis, hippocampus, neural regeneration