中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (5): 463-473.doi: 10.4103/1673-5374.130060

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

拟载脂蛋白E可减少弥漫性脑损伤后神经细胞凋亡

  

  • 收稿日期:2013-11-25 出版日期:2014-03-12 发布日期:2014-03-12
  • 基金资助:

    河北省科学技术研究与发展计划、河北省高等学校科学技术研究重点项目

Apolipoprotein E mimetic peptide protects against diffuse brain injury

Yaning Zhao 1, Jianmin Li 2, Qiqun Tang 1, Junling Gao 1, Changxiang Chen 1, Liwei Jing 1, Pan Zhang 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:2013-11-25 Online:2014-03-12 Published:2014-03-12
  • Contact: Yaning Zhao, College of Rehabilitation, Hebei United University, Tangshan 063000, Hebei Province, China, zyning789@126.com.
  • Supported by:

    This study was supported by Scientific Research and Development Plan of Hebei Province, No. 20276102D; Key Project of Scientific Research in Universities of Hebei Province in China, No. ZD2010106.

摘要:

载脂蛋白E (ApoE)在抑制慢性神经变性过程中发挥重要作用,但其对弥漫性脑损伤后神经功能的影响还不清楚。为探讨载脂蛋白E拟肽对弥漫性脑损伤的作用和作用机制,设计了大鼠弥漫性脑损伤前30min和损伤后3d内7次进行尾静脉注射载脂蛋白E拟肽(0.6mg/kg和1.2mg/kg)给药的实验方案,而后观察脑皮质神经细胞的形态变化,检测ERK1/ 2磷酸化,Bax和细胞色素c蛋白表达,测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,评估损伤后神经细胞的凋亡情况,并测定神经功能变化情况。结果表明,载脂蛋白E拟肽显著减轻弥漫性脑损伤大鼠脑皮质神经细胞凋亡、ERK1/ 2磷酸化、Bax和细胞色素c的表达,并降低MDA水平,提高SOD活性,且这些效应都有剂量依赖性。结果证明载脂蛋白E拟肽能通过抑制ERK1/2/Bax的线粒体介导的凋亡途径防止弥漫性脑损伤引起的细胞凋亡,且能改善学习记忆功能。

关键词: 神经再生, 脑损伤, 载脂蛋白E, 弥漫性脑损伤, 学习记忆, 细胞外信号调节激酶, Bax基因, 线粒体, 活性氧, 细胞凋亡

Abstract:

Apolipoprotein E plays a crucial role in inhibiting chronic neurodegenerative processes. However, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein E mimetic peptide on diffuse brain injury. Apolipoprotein E mimetic peptide was administered into the caudal vein of rats with diffuse brain injury  before and after injury. We found that apolipoprotein E mimetic peptide significantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental findings demonstrate that apolipoprotein E mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mitochondrial apoptotic pathway.

Key words: nerve regeneration, brain injury, apolipoprotein E, diffuse brain injury, learning and memory, extracellular signal-regulated kinase, Bax, mitochondria, reactive oxygen species, apoptosis, Scientific Research and Development Plan of Hebei Province in China, neural regeneration