Cheng Zhe, Li Feng-Wu, Stone Christopher R, Elkin Kenneth, Peng Chang-Ya, Bardhi Redina, Geng Xiao-Kun, Ding Yu-Chuan
Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China.
China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.
Neural Regen Res. 2021 Jun;16(6):1017-1023. doi: 10.4103/1673-5374.300452.
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.
常压氧疗法作为一种简单便捷的手段，可对急性缺血性卒中引发的致病级联反应起到神经保护作用，因而受到关注。然而，常压氧疗法神经保护功效的潜在机制尚未完全阐明。据推测，脑内糖酵解增强参与了常压氧疗法对缺血性卒中的神经保护作用。在本研究中，将Sprague-Dawley大鼠分为两组，一组进行2小时大脑中动脉闭塞，随后再灌注3小时或24小时；另一组进行永久性大脑中动脉闭塞。在缺血发作后2小时，所有大鼠均接受95%氧气的常压氧疗法3小时或吸入室内空气。与吸入室内空气相比，常压氧疗法显著减小了缺血大鼠的梗死体积、神经功能缺损程度，降低了活性氧水平，并增加了三磷酸腺苷的生成。这些变化与糖酵解酶葡萄糖转运蛋白1和3、磷酸果糖激酶1以及乳酸脱氢酶的转录和翻译水平降低有关。此外，常压氧疗法显著降低了单磷酸腺苷激活的蛋白激酶mRNA表达以及磷酸化单磷酸腺苷激活的蛋白激酶蛋白表达。这些研究结果表明，常压氧疗法可通过调节单磷酸腺苷激活的蛋白激酶信号通路并减轻氧化损伤来减少糖酵解，从而在缺血性卒中中发挥神经保护作用。本研究于2018年8月13日获得首都医科大学实验动物伦理委员会批准（批准号：AEEI-2018-033）。
