中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (5): 765-770.doi: 10.4103/1673-5374.182703

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

缺血预适应保护缺血性脑损伤

  

  • 收稿日期:2015-09-12 出版日期:2016-05-20 发布日期:2016-05-20
  • 基金资助:

    国家自然科学基金(81071068,813111290);广东省自然科学基金(2014A030313172)

Ischemic preconditioning protects against ischemic brain injury

Xiao-meng Ma#, Mei Liu#, Ying-ying Liu, Li-li Ma, Ying Jiang, Xiao-hong Chen*   

  1. Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Received:2015-09-12 Online:2016-05-20 Published:2016-05-20
  • Contact: Xiao-hong Chen, M.D., Ph.D., xiaohongchenzssy@aliyun.com.
  • Supported by:

    "This work was supported by grants from the National Natural Science Foundation of China, No. 81071068, the Israel Science Foundation- the National Natural Science Foundation of China (Joint Program), No. 813111290; and the Natural Science Foundation of Guangdong Province in China, No. 2014A030313172."

摘要:

实验假设整合素αvβ3和它的协同激活因子血管内皮生长因子的表达升高在缺血性脑损伤中发挥着重要的神经保护作用。因此,我们将C57BL/6小鼠夹闭双侧颈总动脉5 min,再建立短暂性全脑缺血模型,48 h后再夹闭双侧颈总动脉30 min。组织病理学检测显示,缺血预适应明显减轻了缺血7 d后小鼠海马神经元损伤,缺血预适应减少了缺血24 h后小鼠脑组织中伊文斯兰的渗出。缺血24 h后,缺血预适应+脑缺血小鼠皮质和海马整合素αvβ3、血管内皮生长因子及其受体较单纯脑缺血组均明显下降。结果显示,缺血预适应的脑保护作用与抑制整合素αvβ3和血管内皮生长因子的表达有关。

orcid: 0000-0001-9864-1647(Xiao-meng Ma)

关键词: 神经再生, 脑损伤, 整合素αvβ3, 血管内皮生长因子, 血管内皮生长因子受体, 血管内皮生长因子受体2, 胎肝激酶1, 缺血预适应, 缺血耐受, 全脑缺血, 脑缺血, 脑梗死

Abstract:

"In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia."

Key words: nerve regeneration, brain injury, integrin αVβ3, vascular endothelial growth factor, vascular endothelial growth factor receptor, vascular endothelial growth factor receptor-2, fetal liver kinase 1, ischemic preconditioning, ischemic tolerance, global cerebral ischemia, cerebral ischemia, cerebral infarction, NSFC grant, neural regeneration