中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (13): 1288-1296.doi: 10.4103/1673-5374.137576

• 原著:退行性病与再生 • 上一篇    下一篇

自噬激活可加重血管性痴呆海马区神经元的损伤

  

  • 收稿日期:2014-06-25 出版日期:2014-07-11 发布日期:2014-07-11

Autophagy activation aggravates neuronal injury in the hippocampus of vascular dementia rats

Bin Liu, Jing Tang, Jinxia Zhang, Shiying Li, Min Yuan, Ruimin Wang   

  1. First Department of Neurology, the Affiliated Hospital of Hebei United University, Tangshan, Hebei Province, China
  • Received:2014-06-25 Online:2014-07-11 Published:2014-07-11
  • Contact: Bin Liu, First Department of Neurology, the Affiliated Hospital of Hebei United University, Tangshan 063000, Hebei Province, China, liubintsh@126.com.

摘要:

自噬对血管痴呆过程中海马神经元损伤的影响一直不明确。实验设计了给予血管性痴呆模型大鼠腹腔注射自噬抑制剂渥曼青霉素的方案,探索自噬对血管性痴呆时海马神经元损伤的影响。结果显示血管性痴呆模型大鼠海马CA1区细胞损伤严重,海马CA1区自噬相关蛋白Beclin-1和组织蛋白酶B及微管相关蛋白1轻链3表达增加;渥曼青霉素干预可以抑制上述反应。证实细胞自噬及自噬相关蛋白参与血管性痴呆的病理变化,抑制自噬可有神经保护效应。

关键词: 神经再生, 血管性痴呆, 自噬, Beclin-1, 组织蛋白酶B, 微管相关蛋白1轻链3, 自噬体, 溶酶体, 渥曼青霉素

Abstract:

It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuronal injury in a rat model of vascular dementia. In model rats, hippocampal CA1 neurons were severely damaged, and expression of the autophagy-related proteins beclin-1, cathepsin B and microtubule-associated protein 1 light chain 3 was elevated compared with that in sham-operated animals. These responses were suppressed in animals that received a single intraperitoneal injection of wortmannin, an autophagy inhibitor, prior to model establishment. The present results confirm that autophagy and autophagy-related proteins are involved in the pathological changes of vascular dementia, and that inhibition of autophagy has neuroprotective effects.

Key words: nerve regeneration, vascular dementia, autophagy, beclin-1, cathepsin B, microtbule-associated protein 1 light chain 3, autophagosomes, lysosomes, wortmannin, neural regeneration