基于核磁共振代谢组学分析糖尿病大鼠脑区特异性代谢变化

doi:10.3969/j.issn.2095-9400.2020.05.003

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摘要目的：运用基于核磁共振氢谱的代谢组学方法分析1型糖尿病大鼠多个脑区的代谢变化。方法：取正常大鼠（ n =8）和链脲佐菌素（STZ）诱导的糖尿病大鼠（ n =8）的大脑皮层、纹状体、下丘脑、中脑组织进行核磁共振氢谱代谢组学分析，并通过模式识别和代谢物通路分析考察糖尿病大鼠脑区特异性代谢变化。结果：与对照组大鼠相比，糖尿病大鼠的大脑皮层、纹状体、下丘脑和中脑的代谢模式均发生显著改变。代谢物定量分析显示，与正常大鼠相比，糖尿病大鼠不同脑区具有特异性代谢变化。大脑皮层中乳酸、牛磺酸等代谢物的含量出现显著升高（ P ＜0.05），而N-乙酰天门冬氨酸、胆碱等代谢物的含量显著降低（ P ＜ 0.05）；纹状体中乳酸、牛磺酸等代谢物的含量显著升高（ P ＜0.05），而N-乙酰天门冬氨酸、γ-氨基丁酸等代谢物的含量显著降低（ P ＜0.05）；下丘脑中牛磺酸、肌醇等代谢物的含量出现显著升高（ P ＜0.05），而N乙酰天门冬氨酸、琥珀酸等代谢物的含量显著降低（ P ＜0.05）；中脑中乳酸、肌醇等代谢物的含量显著升高（ P ＜0.05），而N-乙酰天门冬氨酸、γ-氨基丁酸等代谢物的含量显著降低（ P ＜0.05）。结论：1型糖尿病大鼠脑代谢发生显著改变，而且具有脑区特异性的代谢变化，主要涉及能量代谢、神经递质代谢和胆碱代谢。

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	倪志涛
	季慧
	高红昌
	郑宏
	张华杰

关键词 ： , 核磁共振波谱学；糖尿病；脑代谢；代谢组学；大鼠

Abstract：Objective: To investigate the metabolic changes in different brain regions of diabetic rats. Methods: Hippocampus, cortex, hypothalamus and midbrain were dissected from STZ-induced diabetic rats and the age-matched controls. 1H NMR-based metabolomics was performed to detect metabolic profiles in different brain regions, and metabolic characteristics were analyzed by using metabolic pattern recognition and pathway analysis. Results: Diabetic rats had a significant metabolic phenotype in cortex, striatum, hypothalamus and midbrain as compared with age-matched controls. Quantitative results of metabolites showed that diabetic rats had brain region-specific metabolic alterations, compared with controls. Lactate and taurine were distinctly increased in cortex (P<0.05), while the levels of N-acetyl-aspartate and choline were markedly decreased (P<0.05); Lactate and taurine were distinctly increased in striatum (P<0.05), while the levels of N-acetyl-aspartate and GABA were markedly decreased (P<0.05); Taurine and myo-inositol were distinctly increased in hypothalamus (P<0.05), while the levels of N-acetyl-aspartate and Succinate were markedly decreased (P<0.05); Lactate and myo-inositol were distinctly increased in midbrain (P<0.05), while the levels of N-acetyl-aspartate and GABA were markedly decreased (P<0.05). Conclusion: Diabetic rats exhibit region-specific changes in brain metabolism, mainly involving energy metabolism, neurotransmitter metabolism and choline metabolism.

Key words： magnetic resonance spectroscopy diabetesmellitus brain metabolism metabolomics rats

收稿日期: 2019-10-08

基金资助:国家自然科学基金资助项目（21974096，21605115，81771386）。

通讯作者: 张华杰，教授，硕士生导师，Email：zhj@wzmc.edu.cn。

作者简介: 倪志涛（1995-），男，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 10.3969/j.issn.2095-9400.2020.05.003 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I5/364

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