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

Abstract
Figure/Table
References (0)
Related Citation (15)

Download: PDF (1973 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

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

Received: 08 October 2019

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	NI Zhitao
	JI Hui
	GAO Hongchang
	ZHENG Hong
	ZHANG Huajie

URL:

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

[1] American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018 [J]. Diabetes Care, 2018, 41(S1): S13-S27.
[2] EHEHALT S, POPOVIC P, MUNTONI S, et al. Incidence of diabetes mellitus among children of Italian migrants substantiates the role of genetic factors in the pathogenesis of type 1 diabetes[J]. Eur J Pediatr, 2009, 168(5): 613-617.
[3] MILES W R, ROOT H F. Psychologic tests applied to diabetic patients[J]. Arch Intern Med, 1922, 30(6): 767-777.
[4] BRANDS A M, BIESSELS G J, DE HAAN E H, et al. The effects of type 1 diabetes on cognitive performance: a metaanalysis[J]. Diabetes Care, 2005, 28(3): 726-735. [5] DUARTE J M, OSES J P, RODRIGUES R J, et al. Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats[J]. Neuroscience, 2007, 149(2): 382-391.
[6] BECKONERT O, KEUN H C, EBBELS T M, et al. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts[J]. Nat Protoc, 2007, 2(11): 2692-2703.
[7] WISHART D S. Emerging applications of metabolomics in drug discovery and precision medicine[J]. Nat Rev Drug Disc, 2016, 15(7): 473-484.
[8] PUCHADESCARRASCO L, PINEDALUCENA A. Metabolomics in pharmaceutical research and development[J]. Curr Opin Biotech, 2015, 35: 73-77.
[9] HU W, CHENG X, YE X, et al. Ex vivo 1 H nuclear magnetic resonance spectroscopy reveals systematic alterations in cerebral metabolites as the key pathogenetic mechanism of bilirubin encephalopathy[J]. Mol Brain, 2014, 7(1): 1-9.
[10] MACKINNON N, GE W, KHAN A P, et al. Variable reference alignment: an improved peak alignment protocol for NMR spectral data with large intersample variation[J]. AnalChem, 2012, 84(12): 5372-5379.
[11] COEN M, LENZ E M, NICHOLSON J K, et al. An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy[J]. Chem Res Toxicol, 2003, 16(3): 295-303.
[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] ZHAO L C, DONG M J, GAO H C, et al. Metabolomicanalysis identifies lactate as one important pathogenic factor in diabetes-associated cognitive decline rats[J]. Mol Cell Proteomics, 2018, 17(12): 2335-2346.
[15] ZHENG H, ZHAO L C, XIA H H, et al. NMR-based metabolomics 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): 66906697.
[16] 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.
[17] ZHENG H, ZHENGY, WANG D, et al. Analysis of neuronastrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy[J]. Front Cell Neurosic, 2016, 37(1): 332-343.
[18] GUAN M, XIE L, DIAO C, et al. Systemic perturbations of key metabolites in diabetic rats during the evolution of diabetes studied by urine metabonomics[J]. PLoS One, 2013, 8(4): e60409.
[19] GAVAGHAN C L, HOLMES E, LENZ E, et al. An NMRbased metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk: ApfCD mouse[J]. FEBS Lett, 2000, 484(3): 169-174.
[20] NAGAYACH A, PATRO N, PATRO I. Astrocytic and microglial response in experimentally induced diabetic rat brain[J]. Metab Brain Dis, 2014, 29(3): 747-761.
[21] DONG M J, REN M Q, LI C, et al. Analysis of metabolic alterations related to pathogenic process of diabetic encephalopathy rats[J]. Cell Neurosci, 2019, 12: 527-544.
[22] VAN LOON L J, KRUIJSHOOP M, MENHEERE P P, et al. Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes[J]. Diabetes Care, 2003, 26(3): 625-630.
[23] 王丹, 郑涌泉, 赵良才, 等. 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[J]. 温州医科大学学报, 2017, 47(2): 90-95.
[24] LIN Y, FENG W, YANG R H. Diabetes impairs learning performance and affects the mitochondrial function of hippocampal pyramidal neurons[J]. Brain Res, 2011, 1411: 57-64.

[1]	. [J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(8): 0-.