γ-氨基丁酸改善睡眠作用机制的研究进展
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摘要
γ-氨基丁酸(Gamma-aminobutyric acid,GABA)是一种重要的中枢神经系统抑制性神经递质,其拥有良好的水溶性与热稳定性。现已证实,作为小分子量非蛋白质氨基酸的GABA具备食用安全性,并可用于饮料等食品的生产。研究表明,摄入一定量的GABA具备改善机体睡眠质量、降血压等生理功效。本文基于国内外相关文献资料,综述了外源摄入GABA通过肠-脑轴、脑组织透性及其体内代谢物在改善睡眠方面的作用机制。
Gamma-aminobutyric acid( GABA) is a significant inhibitory neurotransmitter in the central nervous system,which performs well water solubility and thermal stability. It has been confirmed that GABA,a small molecular weight non-protein amino acid,possesses food safety and can be used formanufacturing various foods such as beverages. Results showed that the intake of a certain amount of GABA could improve the sleep quality and lower blood pressure in addition to other beneficial effects.Based on domestic and foreign relevant literatures,this article will discuss the mechanism of GABA on improving sleep quality by the effects of GABA on the gut-brainaxis,brain tissue permeability and its metabolites.
Gamma-aminobutyric acid( GABA) is a significant inhibitory neurotransmitter in the central nervous system,which performs well water solubility and thermal stability. It has been confirmed that GABA,a small molecular weight non-protein amino acid,possesses food safety and can be used formanufacturing various foods such as beverages. Results showed that the intake of a certain amount of GABA could improve the sleep quality and lower blood pressure in addition to other beneficial effects.Based on domestic and foreign relevant literatures,this article will discuss the mechanism of GABA on improving sleep quality by the effects of GABA on the gut-brainaxis,brain tissue permeability and its metabolites.
引文
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[2]周小理,赵琳.γ-氨基丁酸的生理功能及在食品中应用的研究进展[J].食品工业,2011(10):58-61.
[3]Diana M,Quílez J,Rafecas M.Gamma-aminobutyric acid as a bioactive compound in foods:A review[J].Journal of Functional Foods,2014,10(3):407-420.
[4]Gottesmann C.Gaba mechanisms and sleep[J].Neuroscience,2002,111(2):231-239.
[5]谢晨,刘臻,赵娜,等.γ-氨基丁酸与睡眠觉醒[J].医药导报,2014,33(5):641-644.
[6]范红华.影响睡眠的因素及睡眠的舒适护理[J].中国社区医师:医学专业,2011,13(4):198-198.
[7]杨菊贤,杜勤.睡眠障碍的诊断和治疗[J].中国全科医学,2003,6(2):165-167.
[8]Thomas R.Insomnia:Definition,prevalence,etiology,and consequences[J].Journal of Clinical Sleep Medicine Jcsm Official Publication of the American Academy of Sleep Medicine,2007,3(5 Suppl):7-10.
[9]Tovargudi1o E,Guevarasalazar J A,Bahenaherrera J R,et al.Novel-substituted heterocyclic gaba analogues.Enzymatic activity against the gaba-at enzyme from pseudomonas fluorescens and in silico molecular modeling[J].Molecules,2018,23(5):1128.
[10]宫琦,梁建辉.γ-羟基丁酸及其前体物质的滥用潜力和现状[J].中国药物依赖性杂志,2012,21(3):161-165.
[11]Boonstra E,de Kleijn R,Colzato L,et al.Neurotransmitters as food supplements:The effects of gaba on brain and behavior[J].Frontiers in Psychology,2015,6:1520.
[12]马燕,段双梅,赵明.富含γ-氨基丁酸食品的研究进展[J].氨基酸和生物资源,2016,38(3):1-6.
[13]Yamatsu A,Yamashita Y,Pandharipande T,et al.Effect of oralγ-aminobutyric acid(gaba)administration on sleep and its absorption in humans[J].Food Science and Biotechnology,2016,25(2):547-551.
[14]Hong K B,Park Y,Suh H J.Sleep-promoting effects of the gaba/5-htp mixture in vertebrate models[J].Behavioural Brain Research,2016,310:36-41.
[15]Abdou A M,Higashiguchi S,Horie K,et al.Relaxation and immunity enhancement effects of gamma-aminobutyric acid(gaba)administration in humans[J].Biofactors,2010,26(3):201-208.
[16]Carabotti M,Scirocco A,Maselli M A,et al.The gut-brain axis:Interactions between enteric microbiota,central and enteric nervous systems[J].Annals of Gastroenterology Quarterly Publication of the Hellenic Society of Gastroenterology,2015,28(2):203-209.
[17]Jongkees B J,Immink M A,Finisguerra A,et al.Transcutaneous vagus nerve stimulation(tvns)enhances response selection during sequential action[J].Frontiers in Psychology,2018,9:1159.
[18]方继良,洪洋,范洋洋,等.经皮电针刺激正常人耳甲迷走神经的功能MRI脑效应研究[J].磁共振成像,2014(6):416-422.
[19]王娴,刘爱华.迷走神经刺激调节睡眠的机制研究进展[J].中风与神经疾病杂志,2015,32(12):1140-1141.
[20]Furness J B.The enteric nervous system and neurogastroenterology[J].Nature Reviews Gastroenterology and Hepatology,2012,9(5):286-294.
[21]Rieder R,Wisniewski P J,Alderman B L,et al.Microbes and mental health:A review[J].Brain Behavior and Immunity,2017,66:9-17.
[22]Egerod K L,Petersen N,Timshel P N,et al.Profiling of g protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms[J].Molecular Metabolism,2018,12:62-75.
[23]Auteri M,Zizzo M G,Serio R.Gaba and gaba receptors in the gastrointestinal tract:From motility to inflammation[J].Pharmacological Research,2015,93:11-21.
[24]Bravo J A,Forsythe P,Chew M V,et al.Ingestion of lactobacillus strain regulates emotional behavior and central gaba receptor expression in a mouse via the vagus nerve[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(38):16050-16055.
[25]王筱君,阎红,李俊.失眠与焦虑、抑郁相关性的临床研究[J].中国误诊学杂志,2009,9(22):5325-5326.
[26]Wu Q,Shah N P.Highγ-aminobutyric acid production from lactic acid bacteria:Emphasis on Lactobacillus brevis as a functional dairy starter[J].Critical Reviews in Food Science and Nutrition,2016,57(17):3661-3672.
[27]Janik R,Thomason L A M,Stanisz A M,et al.Magnetic resonance spectroscopy reveals oral lactobacillus promotion of increases in brain gaba,n-acetyl aspartate and glutamate[J].Neuroimage,2016,125:988-995.
[28]刘伟志,侬宇琴,王伟,等.长期慢性应激人员睡眠质量和人格特征调查[J].第二军医大学学报,2013,34(12):1345-1349.
[29]朱小文,赵红梅,纪美静.GABA对小鼠抗应激能力的影响[J].畜牧与饲料科学,2015(5):18-19.
[30]胡健饶,许宁一.应激对神经内分泌系统影响的研究进展[J].杭州师范大学学报:自然科学版,2002(5):65-68.
[31]Gao Y,Zhou J J,Zhu Y,et al.Chronic unpredictable mild stress induces loss of gaba inhibition in corticotrophin-releasing hormone-expressing neurons through nkcc1 upregulation[J].Neuroendocrinology,2016,104(2):194-208.
[32]Akinci M K,Schofield P R.Widespread expression of gaba(a)receptor subunits in peripheral tissues[J].Neuroscience Research,1999,35(2):145.
[33]徐同锏,钟刚,王希春,等.脂肪包被γ-氨基丁酸对持续热应激奶牛HPA轴和部分免疫指标的影响[J].南京农业大学学报,2014,37(1):127-132.
[34]Farzi A,Fr9hlich E E,Holzer P.Gut microbiota and the neuroendocrine system[J].Neurotherapeutics,2018,15(1):5-22.
[35]Zhe J,Suresh Kumar M,Bryndis B.Gaba is an effective immunomodulatory molecule[J].Amino Acids,2013,45(1):87-94.
[36]Krantis A.Gaba in the mammalian enteric nervous system[J].News in Physiological Sciences,2000,15(6):284-290.
[37]Hong H-K,Maury E,Ramsey K M,et al.Requirement for nf-κb in maintenance of molecular and behavioral circadian rhythms in mice[J].Genes and Development,2018,32:1-13.
[38]Minerwilliams W M,Moughan P J.Intestinal barrier dysfunction:Implications for chronic inflammatory conditions of the bowel[J].Nutrition Research Reviews,2016,29(1):40-59.
[39]Hyland N P,Cryan J F.A gut feeling about gaba:Focus on gabab receptors[J].Frontiers in Pharmacology,2010,1:124.
[40]Mazzoli R,Pessione E.The neuro-endocrinological role of microbial glutamate and gaba signaling[J].Frontiers in Microbiology,2016,7(22):1932.
[41]林智,大森正司.γ-氨基丁酸茶(gabarontea)降血压机理的研究[J].茶叶科学,2001,21(2):153-156.
[42]Abbott N J,Patabendige A A K,Dolman D E M,et al.Structure and function of the blood-brain barrier[J].Neurobiology of Disease,2010,37(1):13-25.
[43]Roberts E,Lowe I P,Guth L,et al.Distribution ofγ-aminobutyric acid and other amino acids in nervous tissue of various species[J].Journal of Experimental Zoology,1958,138(2):313-328.
[44]Kuriyama K,Sze P Y.Blood-brain barrier to h3-gammaaminobutyric acid in normal and amino oxyacetic acid-treated animals[J].Neuropharmacology,1971,10(1):103-108.
[45]Takanaga H,Ohtsuki S,Hosoya K,et al.Gat2/bgt-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier[J].Journal of Cerebral Blood Flow and Metabolism,2001,21(10):1232-1239.
[46]Kakee A,Takanaga H,Terasaki T,et al.Efflux of a suppressive neurotransmitter,gaba,across the blood-brain barrier[J].Journal of Neurochemistry,2001,79(1):110-118.
[47]Al-Sarraf H.Transport of 14 c-γ-aminobutyric acid into brain,cerebrospinal fluid and choroid plexus in neonatal and adult rats[J].Developmental Brain Research,2002,139(2):121-129.
[48]Li Q,Wang S,Xiao W,et al.Bbb:Permeable conjugate of exogenic gaba[J].National Institutes of Health,2017,2(8):4108-4111.
[49]L9scher W,Frey H.H.Transport of gaba at the blood-csf interface[J].Journal of Neurochemistry,1982,38(4):1072-1079.
[50]Helms H C,Abbott N J,Burek M,et al.In vitro models of the blood-brain barrier:An overview of commonly used brain endothelial cell culture models and guidelines for their use[J].Journal of Cerebral Blood Flow and Metabolism Official,2016,36(5):862-890.
[51]Uchida Y,Ohtsuki S,Katsukura Y,et al.Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors[J].Journal of Neurochemistry,2011,117(2):333-345.
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