中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (6): 931-937.doi: 10.4103/1673-5374.208575

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

脑缺血大鼠双侧大脑组织代谢水平的差异

  

  • 收稿日期:2017-05-21 出版日期:2017-06-15 发布日期:2017-06-15
  • 基金资助:

    健康创新人才工程国家支持项目(2016)；国家自然科学基金（81571626，U1404823）；浙江省自然科学基金（ly15h220001）；浙江省医疗卫生研究计划项目（2014kya134）；温州科技局技术项目（y20140731，y20150087）

Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion

Lei Ruan1, Yan Wang1, Shu-chao Chen1, Tian Zhao1, Qun Huang1, Zi-long Hu1, Neng-zhi Xia1, Jin-jin Liu1, Wei-jian Chen1, Yong Zhang2, Jing-liang Cheng2, Hong-chang Gao3, Yun-jun Yang1, Hou-zhang Sun1   

  1. 1 Department of Radiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 2 Department of Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; 3 School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • Received:2017-05-21 Online:2017-06-15 Published:2017-06-15
  • Contact: Hou-zhang Sun or Yun-jun Yang, M.D., shzlxm@163.com or wzfskyyj2011@163.com.
  • Supported by:

    This work was supported by grants from the Health Innovation Talents Project of Zhejiang Province of China, No. 2016; the National Natural Science Foundation of China, No. 81571626, U1404823; the Natural Science Foundation of Zhejiang Province of China, No. LY15H220001; the Medical and Health Research Project of Zhejiang Province of China, No. 2014KYA134; the Wenzhou Bureau of Science and Technology of China, No. Y20140731, Y20150087.

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摘要：

脑缺血不仅使缺血病灶区本身存在病理改变，还可导致一系包括病灶区外与其具有相关神经纤维连接基础的脑区(如对侧大脑半球)的代谢改变，尤其是对侧小脑发生代谢改变的发生率最高。PET、SPECT、PWI和DTI等影像学检查技术多集中在对脑缺血后对侧小脑的血流量、氧代谢率以及摄氧分数等参数指标的检测。实验通过核磁共振波谱（NMR）的代谢组学技术，旨在认识大鼠缺血侧大脑对缺血对侧大脑半球的代谢影响。采用线栓法制作左侧大脑中动脉阻塞的永久性脑缺血大鼠模型，按缺血时间不同(缺血1，3，9，24 h)麻醉处死并取双侧大脑组织进行高分辨磁共振波谱分析显示，大鼠缺血侧大脑Lac，Ala，GABA，Cho和Gly浓度增加，而NAA，Cre，Glu和 Asp浓度降低，说明大鼠脑的缺血24 h内的急性期缺血侧大脑可能存在无氧酵解上调使Lac增加，磷脂代谢异常使Cho增加，神经细胞损伤使NAA降低和神经递质紊乱出现GABA，Gly上升，Glu和Asp降低的应激性改变；而大鼠对侧大脑Lac，Ala，Gly，Cho和Asp浓度增加，而GABA，Glu和Cre浓度降低，说明对侧大脑的应激性改变与缺血侧大脑略有差异。实验证实，从代谢组学角度证实脑缺血不仅可导致缺血脑区本身的代谢水平发生改变，而且对侧脑区的代谢也会受到影响。

ORCID:0000-0001-5463-8358(Hou-zhang Sun)；0000-0002-4493-8477(Yun-jun Yang)

关键词: 神经再生, 脑损伤, 脑缺血, 大脑中动脉栓塞模型, 缺血侧大脑, 缺血对侧大脑, 代谢组学, 核磁共振波谱, Lac, GABA, Cho, 神经机能联系不能

Abstract:

Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions (such as the contralateral cerebral hemisphere). The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis (shown by the increase in lactate), a perturbation of choline metabolism (suggested by the increase in choline), neuronal cell damage (shown by the decrease in N-acetyl aspartate) and neurotransmitter imbalance (evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate) in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a difference in the metabolite changes induced by ischemic injury in the contralateral and ipsilateral cerebral hemispheres. Our findings demonstrate the presence of characteristic changes in metabolites in the contralateral hemisphere and suggest that they are most likely caused by metabolic changes in the ischemic hemisphere.

Key words: nerve regeneration, brain injury, cerebral ischemia, middle cerebral artery occlusion model, ischemic hemisphere, contralateral hemisphere, metabonomics, 1H nuclear magnetic resonance, lactate, choline, γ-aminobutyric acid, diaschisis, neural regeneration