γ-氨基丁酸对LPS介导的机体炎性反应影响的研究进展

doi:10.16431/j.cnki.1671-7236.2018.08.011

摘要/Abstract

摘要：

γ-氨基丁酸（γ-aminobutyric acid，GABA）是哺乳动物体内一种重要的神经性抑制递质，主要分布在中枢神经系统，具有广泛的调控功能。GABA可通过下丘脑-垂体-肾上腺皮质（HPA）轴参与机体稳态的调节，并对外界有害刺激引起的机体炎性反应具有一定的缓解作用。机体在外界应激条件刺激下会引起血液中脂多糖（LPS）含量的升高并激活Toll样受体-4（TLR4）/NF-κB信号通路，引起肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）等的表达增多，最终导致机体产生炎症反应。GABA可在机体发生炎症反应时，通过调节相应炎性因子的表达来降低炎症反应对机体造成的损伤。作者通过对GABA生理学功能与受体类别及GABA在机体发生炎性反应时的作用进行综述，对GABA在机体发生炎性反应时的影响及其与LPS引起的机体炎性反应之间的关系进行分析，为临床上采用GABA治疗机体炎性反应提供理论依据。

关键词: γ -氨基丁酸; 调控; 炎性因子; 炎性反应

Abstract:

γ-aminobutyric acid (GABA) is an important neurotransmitter in mammals,it is mainly distributed in the central nervous system,with a wide range of regulatory functions.GABA can participate in the regulation of body homeostasis through the hypothalamic-pituitary-adrenocortical (HPA) axis,and it has a certain mitigation effect on the inflammatory response caused by harmful stimuli outside.The body will causes the increase of blood lipopolysaccharide (LPS) content under the stimulation of external stress and activate the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway,resulting in the increase of the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and interleukin-8 (IL-8),eventually leading to the body's inflammatory response.GABA can reduce the damage by regulating the expression of the corresponding inflammatory cytokines to the organism when the inflammatory reaction occurs in the body.This article provides a brief overview of the physiological effect of GABA,the types of GABA receptors,and the function of GABA in the inflammatory response to the body,analyzes the effect of GABA on inflammatory response in the body and its relationship with LPS-induced inflammatory response,which provide a theoretical basis for the clinical use of GABA in the treatment of inflammatory response.

Key words: γ-aminobutyric acid (GABA); regulation; inflammatory factors; inflammatory reaction

中图分类号:

S852.4

孙士平, 张成玉, 李和平, 许春梅, 陈佩格, 钟凯, 王月影. γ-氨基丁酸对LPS介导的机体炎性反应影响的研究进展[J]. 《中国畜牧兽医》, 2018, 45(8): 2128-2134.

SUN Shiping, ZHANG Chengyu, LI Heping, XU Chunmei, CHEN Peige, ZHONG Kai, WANG Yueying. Research Progress on Effect of γ-aminobutyric Acid on LPS-mediated Inflammation to the Body[J]. , 2018, 45(8): 2128-2134.

参考文献

[1] 赵欣,葛荣靖,赵士弟.GABA在学习记忆中相关作用的研究进展[J].包头医学院学报,2017,33(5):136-137.ZHAO X,GE R J,ZHAO S D.Research progress on GABA on the relevant function in learning and memory[J].Journal of Baotou Medical College,2017,33(5):136-137.(in Chinese)
[2] BENOTHMAN N,VIEIRA A,COURTNEY M,et al.Long-term GABA administration induces alpha cell-mediated beta-like cell neogenesis[J].Cell,2017,168(1-2):73-85.
[3] MA K,XU A,CUI S,et al.Impaired GABA synthesis,uptake and release are associated with depression-like behaviors induced by chronic mild stress[J]. Translational Psychiatry,2016,6(10):e910.
[4] WANG G Y,ZHU Z M,CUI S,et al.Glucocorticoid induces incoordination between glutamatergic and GABAergic neurons in the amygdala[J].PLoS One,2016,11(11):e0166535.
[5] 陈剑群,汤娜娜,费素娟,等.γ-氨基丁酸对人细胞因子诱导的杀伤细胞增殖的影响[J].中国免疫学杂志,2008,24(5):413-416.CHEN J Q,TANG N N,FEI S J,et al.Effects of γ-aminobutyric acid on proliferation of cytokine-induced killer cells[J].Chinese Journal of Immunology,2008,24(5):413-416.(in Chinese)
[6] 崔莹雪,许焕芳,刘平,等.艾烟对快速老化模型小鼠脑内氨基酸类神经递质含量的影响[J].中国中医药信息杂志,2013,20(10):29-31.CUI Y X,XU H F,LIU P,et al.Effects of moxa smoke on amino acid neurotransmitters in brain of mice with aging-fasting model[J].Chinese Journal of Information on Traditional Chinese Medicine,2013,20(10):29-31.(in Chinese)
[7] 王松涛,曾云贵,王安利.有氧运动对大鼠心血管自主神经中枢Glu能神经和GABA能神经的影响[J].体育科学,2007,27(4):64-71.WANG S T,ZENG Y G,WANG A L.Effect of aerobic exercise on glutamatergic and GABAergic nerves of cardiovascular autonomic nerve center in rats[J].Sports Science,2007,27(4):64-71.(in Chinese)
[8] 孙利净,韩秋月,胡满.γ-氨基丁酸(GABA)受体的研究进展[J].黑龙江畜牧兽医,2016,7:80-83.SUN L J,HAN Q Y,HU M.Research progress on γ-aminobutyric acid (GABA) receptors[J].Heilongjiang Animal Science and Veterinary Medicine,2016,7:80-83.(in Chinese)
[9] 孙利净,胡满.γ-氨基丁酸及其受体生理功能与作用机制的研究进展[J].黑龙江畜牧兽医,2016,1:63-65.SUN L J,HU M.Research progress on γ-aminobutyric acid and its receptor physiological function and mechanism of action[J].Heilongjiang Animal Science and Veterinary Medicine,2016,1:63-65.(in Chinese)
[10] CRUNELLI V,DI G G.Monoamine modulation of tonic GABAA inhibition[J].Reviews in the Neurosciences,2014,25(2):195-206.
[11] LI J,CASTEELS T,FROGNE T,et al.Artemisinins target GABAA receptor signaling and impair α cell identity[J].Cell,2017,168(1-2):86-100.
[12] AZIZBEIGI R,ZARRINDAST M R,AHMADI S.Interaction between gamma-aminobutyric acid type A (GABAA) receptor agents and scopolamine in the nucleus accumbens on impairment of inhibitory avoidance memory performance in rat[J].Behavioural Brain Research,2013,241(2):191-197.
[13] KORPI E R,SINKKONEN S T.GABAA receptor subtypes as targets for neuropsychiatric drug development[J].Pharmacology & Therapeutics,2006,109(1-2):12-32.
[14] FOSTER J D,KITCHEN I,BETTLER B,et al.GABAB receptor subtypes differentially modulate synaptic inhibition in the dentate gyrus to enhance granule cell output[J].British Journal of Pharmacology,2013,168(8):1808-1819.
[15] KHALILOV I,MINLEBAEV M,MUKHTAROV M,et al.Postsynaptic GABA(B) receptors contribute to the termination of giant depolarizing potentials in CA3 neonatal rat hippocampus[J]. Frontiers in Cellular Neuroscience,2017,11:1-11.
[16] HEANEY C F,KINNEY J W.Role of GABAB,receptors in learning and memory and neurological disorders[J].Neuroscience & Biobehavioral Reviews,2016,63:1-28.
[17] KUMAR K,KAUR H,DESHMUKH R.Neuroprotective role of GABA B,receptor modulation against streptozotocin induced behavioural and biochemical abnormalities in rats[J]. Neuroscience,2017,357:67-74.
[18] TYAGI R K,BISHT R,PANT J,et al.Possible role of GABA-B receptor modulation in MPTP induced parkinson's disease in rats[J].Experimental & Toxicologic Pathology,2015,67(2):211-217.
[19] KIRISCHUK S,AKYELI J,IOSUB R,et al.Pre-and postsynaptic contribution of GABAC receptors to GABAergic synaptic transmission in rat collicular slices and cultures[J].European Journal of Neuroscience,2015,18(4):752-758.
[20] MOHAMMADI E,SHAMSIZADEH A,SALARI E,et al.Effect of TPMPA (GABAC receptor antagonist) on neuronal response properties in rat barrel cortex[J].Somatosensory & Motor Research,2017,34(2):108-115.
[21] DOMINGOS-SOUZA G,MESCHIARI C A,BUZELLE S L,et al.Sodium and water intake are not affected by GABAC receptor activation in the lateral parabrachial nucleus of sodium-depleted rats[J].Journal of Chemical Neuroanatomy,2016,74:47-54.
[22] 程伟,文静,戴体俊,等.GABA的镇痛、催眠、遗忘作用及其与GABAA受体的关系[J].中国药理学通报,2008,32(6):783-786.CHENG W,WEN J,DAI T J,et al.Relationship between GABAA receptor and the analgesic,hypnotic and amnesic effects induces by GABA[J].Chinese Pharmacological Bulletin,2008,32(6):783-786.(in Chinese)
[23] COSSETTE P,LIU L,BRISEBOIS K,et al.Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy[J].Nature Genetics,2002,31(2):184-189.
[24] GECCHELE E,MERLIN M,BROZZETTI A,et al.A comparative analysis of recombinant protein expression in different biofactories:Bacteria,insect cells and plant systems[J].Journal of Visualized Experiments,2015,97:e52459
[25] 刁建刚,徐金旺,李古州,等.猫初级视皮层内Glu/GABA表达比率的衰老性变化[J].动物学研究,2009,30(1):38-44.DIAO J G,XU J W,LI G Z,et al.Age-related changes of Glu/GABA expression in the primary visual cortex of cat[J].Zoological Research,2009,30(1):38-44.(in Chinese)
[26] 刘永峰,闵苏,董军,等.异丙酚预先给药对抑郁大鼠电休克后海马Glu和GABA水平的影响[J].中华麻醉学杂志,2009,29(2):121-124.LIU Y F,MIN S,DONG J,et al.Effects of propofol on pretreatment on the levels of glutamate and gamma-aminobutyric acid in hippocampus of mentally depressed rats after electro-convulsive therapy[J].Chinese Journal of Anesthesiology,2009,29(2):121-124.(in Chinese)
[27] 晁成磊,鲁显福,张励才.甲醛致炎痛对大鼠远位触液神经元γ-氨基丁酸表达的影响[J].中国应用生理学杂志,2010,26(1):36-38.CHAO C L,LU X F,ZHANG L C.Formal in-induced pain stimulation induced expression of GABA in the distal cerebrospinal fluid contacting neurons[J].Chinese Journal of Applied Physiology,2010,26(1):36-38.(in Chinese)
[28] 周琦,黄训健,尹时华.水杨酸钠对豚鼠听反应阈值、螺旋神经节形态及GABA、GLU表达的影响[J].山东医药,2012,52(21):30-32.ZHOU Q,HUANG X J,YIN S H.Effect of sodium salicylate on the auditory brainstem response and the morphology,the expressions of γ-aminobutyricacid and glutamate of the spiral ganglion neurons in guinea pigs[J].Shandong Medicine,2012,52(21):30-32.(in Chinese)
[29] 曹承华,贺雅静,高荧苒,等.LPS介导的炎症反应过程及作用机制[J].河南大学学报(医学版),2017,36(1):70-76.CAO C H,HE Y J,GAO Y R,et al.LPS mediated inflammatory response and mechanism[J].Journal of Henan University (Medical Science),2017,36(1):70-76.(in Chinese)
[30] HAGAR J A,POWELL D A,AACHOUI Y,et al.Cytoplasmic LPS activates Caspase-11:Implications in TLR4-independent endotoxic shock[J]. Science,2013,341(6151):1250-1253.
[31] 代蓉,董柳慧,石安华,等.HPA轴抑制大鼠感染性休克模型的建立及四逆汤对该模型的作用[J].云南中医学院学报,2012,35(6):1-6.DAI R,DONG L H,SHI A H,et al.HPA axis suppression and septic shock model established and the effect of Sini Decoction on it[J].Yunnan College of Traditional Chinese Medicine,2012,35(6):1-6.(in Chinese)
[32] QADRI F,RIMMELE F,MALLIS L,et al.Acute hypothalamo-pituitary-adrenal axis response to LPS-induced endotoxemia:Expression pattern of kinin type B1 and B2 receptors[J]. Biological Chemistry,2016,397(2):97-109.
[33] KITAMURA N,AKIYOSHI H,NISHIMURA S,et al.A case of canine neuroblastoma originating from the adrenal medulla complicated by adrenal cortex adenocarcinoma[J].Journal of the Japan Veterinary Medical Association,2016,69(1):41-45.
[34] KUMAR D.Cushing's syndrome[J].Journal of Pharmaceutical Sciences and Research,2015,7:575-576.
[35] 郭晓娜,朱永义,朱科学.生物体内γ-氨基丁酸的研究[J].氨基酸和生物资源,2003,25(2):70-72.GUO X N,ZHU Y Y,ZHU K X.Study on GABA in organism[J].Amino Acids & Biotic Resources,2003,25(2):70-72.(in Chinese)
[36] 徐同锏,钟刚,王希春.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].南京农业大学报,2014,37(1):127-132.XU T J,ZHONG G,WANG X C.Effects of lipid coated γ-aminobutyric acid on HPA axis and some immune indicators of cow in heat stress[J].Journal of Nanjing Agricultural University,2014,37(1):127-132.(in Chinese)
[37] 魏传飞.GABA信号途径参与树突状细胞的抗原递呈及其在DSS诱导的结肠炎中的作用[D].泰安:山东大学,2015.WEI C F.The GABAergic system participates the antigen-presenting of DCs in the intestinal mucosa and plays a role in the DSS-induced enteritis[D].Tai'an:Shandong University,2015.(in Chinese)
[38] ANFUSO C D,OLIVIERI M,FIDILIO A,et al.Gabapentin attenuates ocular inflammation:In vitro and in vivo studies[J].Frontiers in Pharmacology,2017,8(2):1-10.
[39] OSAKA T.Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats[J].Journal of Thermal Biology,2006,31(1-2):229-234.
[40] LI M,QIU L,WANG L,et al.The inhibitory role of γ-aminobutyric acid (GABA) on immunomodulation of pacific oyster crassostrea gigas[J]. Fish & Shellfish Immunology,2016,52:16-22.
[41] 乔圆.氯沙坦对LPS诱导的星形胶质细胞反应性增生的调节作用及机制研究[D].太原:山西医科大学,2016.QIAO Y.The effect and mechanism of losartan on LPS-induced reactive astrogliosis in the mouse hippocampus[D].Taiyuan:Shanxi Medical University,2016.(in Chinese)
[42] 刘云,宋玉蓉,乐国伟,等.葡寡糖对LPS诱导小鼠氧化应激与炎症反应调节作用的研究[J].天然产物研究与开发,2011,23(2):240-245.LIU Y,SONG Y R,LE G W,et al.Effect of glucose oligosaccharides on the oxidative stress and inflammatory response under LPS induce[J].Natural Product Research and Development,2011,23(2):240-245.(in Chinese)
[43] 袁莲芳.参与LPS诱导的免疫应激反应神经元上GABA受体的表达[D].西安:第四军医大学,2008.YUAN L F.Expression of GABA receptors in neurons involved in immune-stimulating stress induced by lipopolysaccharide[D].Xi'an:The Fourth Military Medical University,2008.(in Chinese)