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轻度运动不会引起乳酸升高,通过调节沙鼠海马中的 microRNA 诱导缺血耐受。

Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus.

机构信息

Department of General Medicine, Kagawa University Faculty of Medicine, Miki, Japan; Department of Neurology, Kagawa University Faculty of Medicine, Miki, Japan.

Department of Neurology, Kagawa University Faculty of Medicine, Miki, Japan.

出版信息

Brain Res. 2020 Apr 1;1732:146710. doi: 10.1016/j.brainres.2020.146710. Epub 2020 Feb 6.

DOI:10.1016/j.brainres.2020.146710
PMID:32035888
Abstract

Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070-2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs.

摘要

先前,我们在沙土鼠全脑短暂缺血模型中研究了耐缺血运动的可能神经保护作用,并在不同条件下评估了组织学、特定蛋白表达和脑功能。本研究在沙土鼠脑缺血/再灌注损伤模型中研究了无乳酸升高的轻度运动的神经保护作用。通过双侧颈总动脉闭塞 5 分钟诱导全脑短暂缺血。一组动物在缺血诱导前进行跑步机运动。评估海马神经元损伤和 miRNA 表达以及行为缺陷和血浆乳酸水平。轻度运动抑制了海马神经元的丢失并保持了短期记忆。此外,14 种 miRNA(mmu-miR-211-3p、-327、-451b、-711、-3070-3p、-3070-2-3p、-3097-5p、-3620-5p、-6240、-6916-5p、-6944-5p、7083-5p、-7085-5p 和 -7674-5p)上调,6 种 miRNA(mmu-miR-148b-3p、-152-3p、-181c-5p、-299b-5p、-455-3p 和 -664-3p)下调,这是由于缺血所致。然而,当动物在缺血事件前进行轻度运动时,这些 miRNA 的表达保持不变。差异表达的 miRNA 调节多个生物学过程,如炎症、代谢和细胞死亡。这些发现表明,轻度运动通过调节海马 miRNA 减少短暂缺血后神经元死亡和行为缺陷。

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