核磁共振氢谱检测糖尿病不同发病阶段额叶和枕叶的代谢变化

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摘要目的：运用基于核磁共振氢谱（1H NMR）的代谢组学方法分析1型糖尿病大鼠不同发病阶段额叶和枕叶2个脑区的代谢变化。方法：取正常大鼠（n=22）和链脲0佐菌素（STZ）诱导的糖尿病大鼠发病1周（n=8）、5周（n=7）、9周（n=7）的额叶和枕叶组织进行1H NMR检测，并结合多元模式识别和代谢物定量分析阐述代谢特征。结果：糖尿病发病各个时期，额叶和枕叶的代谢模式均发生显著改变。与正常大鼠相比，代谢物乳酸（Lac）、牛磺酸（Tau）、肌醇（m-Ins）含量随着糖尿病的发展明显升高；而N-乙酰天冬氨酸（NAA）、天冬氨酸（Asp）、琥珀酸（Suc）等的含量显著降低。结论：额叶和枕叶的代谢变化相似，且均发生于糖尿病早期，主要涉及能量代谢紊乱、谷氨酸-谷氨酰胺-γ-氨基丁酸（Glu-Gln-GABA）循环抑制、渗透压调节增强。

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	王丹
	郑涌泉
	赵良才
	郑宏
	高红昌
	张华杰

关键词 ：糖尿病, 能量代谢, 额叶, 枕叶, 核磁共振氢谱, 大鼠

Abstract： To investigate the metabolic changes of frontal lobe and occipital lobe in different stages of diabetes. Methods: The frontal lobe and occipital lobe were dissected from the 1-week, 5-week and 9-week diabetic rats and the age-matched controls. 1H NMR-based metabonomics combined with multivariate pattern recognition analysis and quantitative analysis were used to study the metabolic characteristics. Results: The metabolic patterns of frontal lobe and occipital lobe were significantly changed in different stages of diabetes. Compared to the controls, lactate, taurine and myo-inositol were distinctly increased both in frontal lobe and occipital lobe with the development of diabetes, while the levels of N-acetyl-aspartate, aspartate and succinate were markedly decreased. Conclusion: The metabolic changes in frontal lobe and occipital lobe are similar, and occurr in the early stage of diabetes. The metabolic changes mainly focus around the disordered energy metabolism, inhibit Glu-Gln-GABA cycle and increas osmoregulation.

Key words： diabetes mellitus energy metabolism frontal lobe occipital lobe 1H NMR rats

收稿日期: 2016-05-17

基金资助:浙江省药学重中之重一级学科开放基金（YKFJ2-003）；浙江省自然科学基金资助项目（LY14H090014，LY15H180010）；高等学校博士学科点专项科研基金新教师类资助课题（20133321 120006）

通讯作者: 张华杰，教授，硕士生导师，Email：zhanghuajie116@sina.com

作者简介: 王丹（1991-），女，浙江嘉兴人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I2/90

[1] CHEN J, CUI X, ZACHAREK A, et al. White matter damage and the effect of matrix metalloproteinases in type 2 diabetic mice after stroke[J]. Stroke, 2011, 42(2): 445-452.
[2] 黄微, 曹子玉. STZ诱导大鼠1型糖尿病进行性脑萎缩的磁共振成像及组织化学研究[J]. 波谱学杂志, 2015, 32(3): 439-449.
[3] WEINSTEIN G, MAILLARD P, HIMALI J J, et al. Glucose indices are associated with cognitive and structural brain measures in young adults[J]. Neurology, 2015, 84(23): 2329-2337.
[4] GAO H C, ZHU H, SONG C Y, et al. Metabolic changes detected by ex vivo high resolution 1H NMR spectroscopy in the striatum of 6-OHDA-induced Parkinson’s rat[J]. MolNeurobiol, 2013, 47(1): 123-130.
[5] LIU K, YE X J, HU W Y, et al. Neurochemical changes in the rat occipital cortex and hippocampus after repetitive and profound hypoglycemia during the neonatal period: an ex vivo 1H magnetic resonance spectroscopy study[J]. MolNeurobiol, 2013, 48(3): 729-736.
[6] WANG N, ZHAO L C, ZHENG Y Q, et al. Alteration of interaction between astrocytes and neurons in different stages of diabetes: a nuclear magnetic resonance study using [113C] Glucose and [2-13C] Acetate[J]. Mol Neurobiol, 2015, 51(3): 843-852.
[7] ZHENG Y Q, YANG Y J, DONG B J, et al. Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline [J]. Mol Brain, 2016, 9: 40.
[8] PSIHOGIOS N G, GAZI I F, ELISAF M S, et al. Gender-related and age-related urinalysis of healthy subjects by NMR-based metabonomics[J]. NMR Biomed, 2008, 21(3): 195-207.
[9] 魏婷婷, 郑涌泉, 王慧, 等. 2型糖尿病小鼠小脑代谢物的1H NMR研究[J]. 温州医科大学学报, 2015, 45(2): 119-122.
[10] ZHENG H, ZHAO L C, XIA H H, et al. NMR-based me-tabolomics reveal a recovery from metabolic changes in the striatum of 6-OHDA-induced rats treated with basic fibroblast growth factor[J]. Mol Neurobiol, 2016, 53(10): 6690-6697.
[11] GAO H C, XIANG Y, SUN N L, et al. Metabolic changes in rat prefrontal cortex and hippocampus induced by chronic morphine treatment studied ex vivo by high resolution 1H
NMR spectroscopy[J]. Neurochem Int, 2007, 50(2): 386-394.
[12] MAGISTRETTI P J, ALLAMAN I. A cellular perspective on brain energy metabolism and functional imaging[J]. Neuron, 2015, 86(4): 883-901.
[13] 方永奇, 莫镇涛. 脑能量代谢调节机制研究新进展[J]. 广州中医药大学学报, 2011, 28(3): 328-331.
[14] BRAND A, RICHTER-LANDSBERG C, LEIBFRITZ D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells[J]. Dev Neurosci, 1993, 15(3-5): 289-298.
[15] SARTORIUS A, LUGENBIEL P, MAHLSTEDT M M, et al. Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain[J]. J Neurosci Methods, 2008, 172(2): 215-219.
[16] 李春霞, 王亚强, 潘文举, 等. 长期慢性强迫游泳应激抑郁模型大鼠前额叶脑代谢物的1H NMR研究[J]. 武汉大学学报(理学版), 2008, 54(4): 451-456.
[17] SAHIN I, ALKAN A, KESKIN L, et al. Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus[J]. J Diabetes Complications, 2008,22(4): 254-260.
[18] STRZELECKI D, GRZELAK P, PODGORSKI P, et al. Comparison of metabolite concentrations in the left dorsolateral prefrontal cortex, the left frontal white matter, and the
left hippocampus in patients in stable schizophrenia treated with antipsychotics with or without antidepressants. 1H-NMR spectroscopy study[J]. Int J Mol Sci, 2015, 16(10): 24387-24402.
[19] MANGIA S, KUMAR A F, MOHEET A A, et al. Neuro chemical profile of patients with type 1 diabetes measure by 1H-MRS at 4 T[J]. J Cereb Blood Flow Metab, 2013, 33(5): 754-759.
[20] ZHANG M, SU X, ZHANG Z, et al. Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy[J]. Int J Neurosci, 2014, 124(1): 37-41.