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缺氧、冬眠与神经保护:小鼠实验研究

Hypoxia, hibernation and Neuroprotection: An Experimental Study in Mice.

作者信息

Ren Changhong, Li Sijie, Rajah Gary, Shao Guo, Lu Guowei, Han Rongrong, Huang Qingjian, Li Haiyan, Ding Yuchuan, Jin Kunlin, Ji Xunming

机构信息

1Beijing Key Laboratory of Hypoxia Translational Medicine, Beijing 100053, China.

2Center of Stroke, Beijing Institute for Brain Disorder, Beijing 100069, China.

出版信息

Aging Dis. 2018 Aug 1;9(4):761-768. doi: 10.14336/AD.2018.0702. eCollection 2018 Aug.

DOI:10.14336/AD.2018.0702
PMID:30090664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6065299/
Abstract

Hibernation is a unique physiological state that evolved to survive periods of food shortages. It is characterized by profound decreases in metabolic rate, body temperature and physiological functions. Studies have shown that animals in hibernation can resist neurological damage. Here, we aimed to study whether hypoxia can induce a hibernation-like state in a traditionally non-hibernating animal and whether it is neuroprotective. All procedures were conducted according to international guidelines on laboratory animal safety. Mice C57BL/6 (19-21g) were placed into a 125 mL jar with fresh air and the jar was sealed with a rubber plug. For each run, the tolerance limit was judged by the animals' appearance for "air hunger". The animal was removed from the jar as soon as its first gasping breath appeared and was moved to another fresh-air-containing jar of similar volume. This procedure was performed in four runs. The hypoxia exposure significantly decreased oxygen (O) consumption, carbon dioxide (CO) production, respiratory rate and heart rate. Meanwhile, rectal temperature reached a minimum of 12.7±2.56°C, which is lower than a wide range of ambient temperatures. The mimicked hibernation decreased the infarct size in a focal cerebral ischemia mouse model. Our findings suggest the possibility of inducing suspended animation-like hibernation states for medical applications post injury.

摘要

冬眠是一种独特的生理状态,其进化目的是在食物短缺时期生存下来。它的特点是代谢率、体温和生理功能大幅下降。研究表明,处于冬眠状态的动物能够抵抗神经损伤。在此,我们旨在研究缺氧是否能在传统上不冬眠的动物中诱导出类似冬眠的状态,以及这种状态是否具有神经保护作用。所有实验步骤均按照国际实验动物安全指南进行。将C57BL/6小鼠(19 - 21克)放入一个装有新鲜空气的125毫升广口瓶中,并用橡胶塞密封。每次实验时,根据动物出现“空气饥饿”的表现来判断耐受极限。一旦动物出现第一次喘息呼吸,就将其从广口瓶中取出,并转移到另一个装有新鲜空气的、体积相似的广口瓶中。这个过程进行了四次。缺氧暴露显著降低了氧气(O)消耗、二氧化碳(CO)产生、呼吸频率和心率。同时,直肠温度最低达到12.7±2.56°C,低于广泛的环境温度范围。模拟冬眠减少了局灶性脑缺血小鼠模型中的梗死面积。我们的研究结果表明,在受伤后诱导类似假死的冬眠状态用于医学应用具有可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/44b0cc581dc1/ad-9-4-761-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/aa3c0028de2d/ad-9-4-761-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/eb1c225ba235/ad-9-4-761-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/44b0cc581dc1/ad-9-4-761-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/aa3c0028de2d/ad-9-4-761-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/eb1c225ba235/ad-9-4-761-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cf/6065299/44b0cc581dc1/ad-9-4-761-g3.jpg

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本文引用的文献

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Brain Circ. 2017 Oct-Dec;3(4):186-198. doi: 10.4103/bc.bc_28_17. Epub 2017 Dec 29.
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Effects of Therapeutic Hypothermia Combined with Other Neuroprotective Strategies on Ischemic Stroke: Review of Evidence.治疗性低温联合其他神经保护策略对缺血性脑卒中的影响:证据综述
Aging Dis. 2018 Jun 1;9(3):507-522. doi: 10.14336/AD.2017.0628. eCollection 2018 Jun.
3
Mild Therapeutic Hypothermia Protects the Brain from Ischemia/Reperfusion Injury through Upregulation of iASPP.
轻度治疗性低温通过上调iASPP保护大脑免受缺血/再灌注损伤。
Aging Dis. 2018 Jun 1;9(3):401-411. doi: 10.14336/AD.2017.0703. eCollection 2018 Jun.
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HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice.HCN通道对发育中小鼠静脉麻醉药的敏感性有影响。
Oncotarget. 2018 Feb 5;9(16):12907-12917. doi: 10.18632/oncotarget.24408. eCollection 2018 Feb 27.
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Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation.脑缺血通过 Notch1 信号激活诱导梗死周边区血管生成。
Exp Neurol. 2018 Jun;304:30-40. doi: 10.1016/j.expneurol.2018.02.013. Epub 2018 Feb 23.
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Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization.姜黄素通过调节小胶质细胞/巨噬细胞极化预防缺血性中风。
Front Aging Neurosci. 2017 Jul 21;9:233. doi: 10.3389/fnagi.2017.00233. eCollection 2017.
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