中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1017-1023.doi: 10.4103/1673-5374.300452

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

常压氧可减轻缺血性脑卒中的高糖酵解

  

  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:

    国家自然科学基金（81802231，81871838），北京市人才工程项目（201800082595G485），北京市通州区科技计划（KJ2019CX004）

Normobaric oxygen therapy attenuates hyperglycolysis in ischemic stroke

Zhe Cheng1, Feng-Wu Li2, Christopher R. Stone3, Kenneth Elkin3, Chang-Ya Peng3, Redina Bardhi3, Xiao-Kun Geng1, 2, 3, *, Yu-Chuan Ding2, 3, *   

  1. 1 Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China;  2 China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China;  3 Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Xiao-Kun Geng, MD, xgeng@ccmu.edu.cn; Yu-Chuan Ding, MD, PhD, yding@med.wayne.edu.
  • Supported by:
    This study was partially supported by the National Natural Science Foundation of China, Nos. 81802231 (to FWL), 81871838 (to XKG), the Organization Department of Beijing Talents Project, No. 2018000082595G485 (to FWL), and the Science and Technology Plan of Beijing Tongzhou District of China, No. KJ2019CX004 (to ZC and FWL).

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摘要：

常压氧作为一种能对急性缺血性脑卒中病理性级联反应发挥神经保护简便方法已引起关注，但是常压氧的神经保护机制尚未阐明。实验假设脑卒中大脑中高糖酵解可能参与常压氧对缺血性脑卒中的神经保护作用。实验对SD大鼠行2h大脑中动脉闭塞继而3或24h的再灌注，或行永久性大脑中动脉闭塞。缺血2h后，大鼠接受95%常压氧治疗3h。结果发现，与单纯空气相比，常压氧能显著降低缺血大鼠的脑梗死体积，改善神经功能，并减少损伤侧脑组织中活性氧含量，同时增加三磷酸腺苷生成量。上述变化与损伤侧脑组织中高糖酵解酶葡萄糖转运蛋白1和3，磷酸果糖激酶1和乳酸脱氢酶的转录和翻译水平降低有关。此外，常压氧还抑制了AMPK mRNA表达和磷酸化AMPK蛋白的表达。结果表明，常压氧可通过调节AMPK信号传导通路和氧化损伤来减少高糖酵解，从而对缺血性脑卒中发挥神经保护作用。实验于2018年8月13日首都医科大学机构动物伦理委员会批准，批准号AEEI-2018-033。

https://orcid.org/0000-0001-5358-1660 (Yu-Chuan Ding)

关键词: 氧气, 氧化应激, 神经保护, 脑卒中, 修复, 恢复, 通路, 大鼠

Abstract: Normobaric oxygen therapy has gained attention as a simple and convenient means of achieving neuroprotection against the pathogenic cascade initiated by acute ischemic stroke. The mechanisms underlying the neuroprotective efficacy of normobaric oxygen therapy, however, have not been fully elucidated. It is hypothesized that cerebral hyperglycolysis is involved in the neuroprotection of normobaric oxygen therapy against ischemic stroke. In this study, Sprague-Dawley rats were subjected to either 2-hour middle cerebral artery occlusion followed by 3- or 24-hour reperfusion or to a permanent middle cerebral artery occlusion event. At 2 hours after the onset of ischemia, all rats received either 95% oxygen normobaric oxygen therapy for 3 hours or room air. Compared with room air, normobaric oxygen therapy significantly reduced the infarct volume, neurological deficits, and reactive oxygen species and increased the production of adenosine triphosphate in ischemic rats. These changes were associated with reduced transcriptional and translational levels of the hyperglycolytic enzymes glucose transporter 1 and 3, phosphofructokinase 1, and lactate dehydrogenase. In addition, normobaric oxygen therapy significantly reduced adenosine monophosphate-activated protein kinase mRNA expression and phosphorylated adenosine monophosphate-activated protein kinase protein expression. These findings suggest that normobaric oxygen therapy can reduce hyperglycolysis through modulating the adenosine monophosphate-activated protein kinase signaling pathway and alleviating oxidative injury, thereby exhibiting neuroprotective effects in ischemic stroke. This study was approved by the Institutional Animal Investigation Committee of Capital Medical University (approval No. AEEI-2018-033) on August 13, 2018.  

Key words: neuroprotection, oxidative stress, oxygen, pathways, rat, recovery, repair, stroke