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| 基于核磁共振技术研究脑缺血再灌注大鼠脑皮质代谢物组水平变化的分子机制 |
| 马夏珍1,张天舒1,阮志2,黄瑾1*,张乃霞3,刘霞3 |
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(1. 华东理工大学药学院上海市新药筛选重点实验室, 上海 200237;
2. 中国科学院上海药物研究所受体结构与功能重点实验室, 上海 201203;
3. 中国科学院上海药物研究所分析化学研究室, 上海 201203
*通信作者) |
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| 摘要: |
| 目的 研究脑卒中大鼠脑皮质代谢物组水平与脑缺血再灌注时间的关系，探讨缺血再灌注损伤导致的脑皮质代谢紊乱的分子机制。方法 采用大脑中动脉闭塞法（MCAO）制备大鼠局灶性左脑缺血的脑卒中模型，运用基于核磁共振的代谢物组分析技术，研究MCAO大鼠脑缺血再灌注3、6、24 h时左脑皮质代谢物水平变化。结果 大鼠左脑皮质缺血再灌注3 h时出现能量不足、糖酵解加剧、神经递质紊乱等代谢途径的改变，再灌注6 h时因机体自身调节作用，上述现象均有所缓解；然而再灌注24 h时，能量代谢、无氧酵解、神经递质代谢紊乱等均加重。结论 再灌注不同时间点引起了不同程度的大脑皮质代谢紊乱，该结果将有助于探索脑缺血再灌注损伤的病理分子机制，可为临床上调控脑卒中发生后不同时间点的代谢紊乱提供理论基础。 |
| 关键词: 核磁共振 卒中 脑缺血 再灌注损伤 代谢紊乱 分子机制 |
| DOI：10.16781/j.0258-879x.2016.11.1338 |
| 投稿时间：2016-06-21修订日期：2016-09-23 |
| 基金项目:国家自然科学基金（21272246），国家重点基础研究发展计划（“973”计划，2013CB910900）. |
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| Molecular mechanism of metabolic changes in rat cerebral cortex after cerebral ischemia-reperfusion: an NMR-based study |
| MA Xia-zhen1,ZHANG Tian-shu1,RUAN Zhi2,HUANG Jin1*,ZHANG Nai-xia3,LIU Xia3 |
(1. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China;
2. Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3. Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
*Corresponding authors.) |
| Abstract: |
| Objective To investigate the relationship between metabolite levels and the time of cerebral ischemia-reperfusion in the left cortex of rats, so as to explore the molecular mechanism of cortical metabolic disorders induced by ischemia-reperfusion injury. Methods Stroke models of focal cerebral ischemia in rats were established by middle cerebral artery occlusion (MCAO). Then a nuclear magnetic resonance (NMR)-based metabolome analytical approach was carried out to analyze the metabolite levels in the left cortex of MCAO rats at different time points (3, 6, and 24 h) after reperfusion. Results Some changes of metabolic pathways, such as energy deficiency, glycolysis aggravation, and neurotransmitter disorders, were observed in the left cortex of MCAO rats at 3 h after reperfusion. All the above-mentioned disorders were alleviated by the autoregulation at 6 h after reperfusion. However, the forementioned metabolic disturbances became severe after 24-hour reperfusion. Conclusion Our results suggest that different extents of metabolic disturbance appears in the cortex at different time points after reperfusion, which might help to understand the molecular mechanism of cerebral ischemia-reperfusion injury, providing reference for regulating metabolic disorders at different time points after stroke in clinic. |
| Key words: nuclear magnetic resonance stroke brain ischemia reperfusion injuries metabolic disorders molecular mechanism |
