表没食子儿茶素没食子酸酯对慢性温和不可预知应激抑郁小鼠的保护作用
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摘要
目的研究表没食子儿茶素没食子酸酯(EGCG)的抗抑郁作用。方法制备慢性温和不可预知应激(CUMS)刺激小鼠抑郁模型;通过旷场实验、体质量、糖水偏爱率、强迫游泳实验和悬尾实验静止时间等指标考察EGCG的抗抑郁作用;检测血清皮质酮(CORT)、促肾上腺皮质激素(ACTH)水平;检测海马组织丙二醛(MDA)水平及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性;实时定量PCR(RT-PCR)检测海马组织中吲哚胺2,3-双加氧酶(IDO)、白细胞介素-1β(IL-1β)、IL-6 m RNA表达。结果 EGCG改善小鼠抑郁状态行为活动;降低血清CORT、ACTH水平;减少海马中MDA的量,提高SOD、GSH-Px活性,下调IDO、IL-6及IL-1βm RNA表达。结论 EGCG可改善小鼠抑郁症状,其机制可能与降低血清中CORT、ACTH水平,抑制海马中MDA的生成,促进SOD、GSH-Px分泌,以及下调IDO、IL-6、IL-1β基因表达有关。
Objective To observe the protective effects of epigallocatechin gallate(EGCG) on the depression. Methods The depressive mice model induced by chronic unpredictable mild stress(CUMS) was established. The behavioristics of the mice exposed to various stress were tested form the open-field, body weight, sucrose preference, forced swimming and tail suspension test for investigating the antidepressant effect of EGCG. Meanwhile, serum CORT, ACTH levels, and the hippocampus MDA, SOD and GSH-Px were estimated. The m RNA expression of indoleamine 2,3-dioxygenase(IDO), IL-1β, and IL-6 in the hippocampus tissue were detected by RT-PCR. Results EGCG improved the behavioristics of depressive mice, however, it ameliorated the serum CORT and ACTH levels. Moreover, EGCG increased the activity of SOD and GSH-Px, and reduced MDA, IDO, IL-6, and IL-1β expression on the m RNA levels in the hippocampus tissue. Conclusion EGCG could attenuate depressive status of mice, and the underlying mechanism may related to the reduction of serum CORT and ACTH, down-regulation of MDA, IL-1β, IL-6, and IDO, and up-regulation of SOD and GSH-Px in hippocampus.
Objective To observe the protective effects of epigallocatechin gallate(EGCG) on the depression. Methods The depressive mice model induced by chronic unpredictable mild stress(CUMS) was established. The behavioristics of the mice exposed to various stress were tested form the open-field, body weight, sucrose preference, forced swimming and tail suspension test for investigating the antidepressant effect of EGCG. Meanwhile, serum CORT, ACTH levels, and the hippocampus MDA, SOD and GSH-Px were estimated. The m RNA expression of indoleamine 2,3-dioxygenase(IDO), IL-1β, and IL-6 in the hippocampus tissue were detected by RT-PCR. Results EGCG improved the behavioristics of depressive mice, however, it ameliorated the serum CORT and ACTH levels. Moreover, EGCG increased the activity of SOD and GSH-Px, and reduced MDA, IDO, IL-6, and IL-1β expression on the m RNA levels in the hippocampus tissue. Conclusion EGCG could attenuate depressive status of mice, and the underlying mechanism may related to the reduction of serum CORT and ACTH, down-regulation of MDA, IL-1β, IL-6, and IDO, and up-regulation of SOD and GSH-Px in hippocampus.
引文
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[26]张心华,徐珞.抑郁症及焦虑症病人血浆SOD活性和MDA含量的变化[J].齐鲁医学杂志,1997,12(4):157-158.
[27]Zhao Z,Wang W,Guo H,et al.Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis,in chronic variable stress induced depression model rats[J].Behav Brain Res,2008,194(1):108-113.
[28]Raedler T J.Inflammatory mechanisms in major depressive disorder[J].Current Opin Psych,2011,24(6):519-525.
[29]Catenadell'Osso M,Bellantuono C,Consoli G,et al.Inflammatory and neurodegenerative pathways in depression:A new avenue for antidepressant development?[J].Current Med Chem,2011,18(2):245-255.
[30]Song C,Wang H.Cytokines mediated inflammation and decreased neurogenesis in animal models of depression[J].Progr Neuro-psychopharmacol Biol Psych,2011,35(3):760-768.
[31]Corona A W,Norden D M,Skendelas J P,et al.Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor(CX(3)CR1)-deficient mice[J].Brain Behav Imm,2013,31(24):134-142.
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[35]Suganuma M,Okabe S,Oniyama M,et al.Wide distribution of[3H](-)-epigallocatechin gallate,a cancer preventive tea polyphenol,in mouse tissue[J].Carcinogenesis,1998,19(10):1771-1776.
[2]Duman R S,Malberg J,Nakagawa S.Regulation of adult neurogenesis by psychotropic drugs and stress[J].JPharmacol Exper Therap,2001,299(2):401-407.
[3]Rutledge R B,Moutoussis M,Smittenaar P,et al.Association of neural and emotional impacts of reward prediction errors with major depression[J].JAMA Psych,2017,74(8):790-797.
[4]Ledford H.Medical research:If depression were cancer[J].Nature,2014,515(7526):182-184.
[5]Wulsin L,Alterman T,Timothy B P,et al.Prevalence rates for depression by industry:a claims database analysis[J].Soc Psych Psych Epidemiol,2014,49(11):1805-1821.
[6]Kotzalidis G D,Rapinesi C,Savoja V,et al.Neurobiological evidence for the primacy of mania hypothesis[J].Curr Neuropharmacol,2017,15(3):339-352.
[7]宛晓春.茶叶生物化学[M].北京:中国农业出版社,2003.
[8]Nanjo F,Goto K,Seto R,et al.Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical[J].Free Rad Biol Med,1996,21(6):895-902.
[9]Kumamoto M,Sonda T,Nagayama K,et al.Effects of p H and metal ions on antioxidative activities of catechins[J].J Agric Chem Soc Japan,2001,65(1):126-132.
[10]Zaveri N T.Green tea and its polyphenolic catechins:medicinal uses in cancer and noncancer applications[J].Life Sci,2006,78(18):2073-2080.
[11]Nagle D G,Ferreira D,Zhou Y D.Epigallocatechin-3-gallate(EGCG):Chemical and biomedical perspectives[J].Phytochemistry,2006,67(17):1849-1855.
[12]王苗苗,韩杰,娄海燕.表没食子儿茶素没食子酸酯对心脑血管缺血再灌注损伤保护作用机制的研究进展[J].中草药,2014,45(18):2732-2736.
[13]Rondanelli M,Opizzi A,Solerte S B,et al.Administration of a dietary supplement(N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula)enhances compliance with diet in healthy overweight subjects:a randomized controlled trial[J].British J Nutr,2009,101(3):457-464.
[14]赵思俊,赵晓喆,向欢,等.基于代谢通路调控的沙棘籽油抗抑郁作用机制研究[J].中草药,2017,48(13):2682-2690.
[15]杨帅,潘晔,宋彦奇,等.交泰丸对抑郁大鼠行为学及脑内单胺类神经递质的影响[J].中草药,2016,47(23):4218-4223.
[16]李晓秋,许晶.抑郁动物模型的研究进展[J].中华精神科杂志,2002,35(3):184-186.
[17]Gr?nli J,Murison R,Fiske E,et al.Effects of chronic mild stress on sexual behavior,locomotor activity and consumption of sucrose and saccharine solutions[J].Physiol Behav,2005,84(4):571-577.
[18]Bekris S,Antoniou K,Daskas S,et al.Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains[J].Behav Brain Res,2005,161(1):45-59.
[19]Katz R J,Roth K A,Carroll B J.Acute and chronic stress effects on open field activity in the rat:Implications for a model of depression[J].Neurosci Biobehav Rev,1981,5(2):247-251.
[20]Cryan J F,Valentino R J,Lucki I.Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test[J].NeurosciBiobehav Rev,2005,29(4):547-569.
[21]Flandreau E I,Ressler K J,Owens M J,et al.Chronic overexpression of corticotropin-releasing factor from the central amygdala produces HPA axis hyperactivity and behavioral anxiety associated with gene-expression changes in the hippocampus and paraventricular nucleus of the hypothalamus[J].Psychoneuroendocrinology,2012,37(1):27-38.
[22]Xu Y,Ku B,Tie L,et al.Curcumin reverses the effects of chronic stress on behavior,the HPA axis,BDNF expression and phosphorylation of CREB[J].Brain Res,2006,1122(1):56-64.
[23]Mizoguchi K,Shoji H,Ikeda R,et al.Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopaminergic neurotransmission[J].Pharmacol Biochem Behav,2008,91(1):170-175.
[24]Fumagalli F,Molteni R,Racagni G,et al.Stress during development:Impact on neuroplasticity and relevance to psychopathology[J].Progr Neurobiol,2007,81(4):197-217.
[25]Lanfumey L,Mongeau R,Cohen-Salmon C,et al.Corticosteroid-serotonin interactions in the neurobiological mechanisms of stress-related disorders[J].Neurosci Biobehav Rev,2008,32(6):1174-1184.
[26]张心华,徐珞.抑郁症及焦虑症病人血浆SOD活性和MDA含量的变化[J].齐鲁医学杂志,1997,12(4):157-158.
[27]Zhao Z,Wang W,Guo H,et al.Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis,in chronic variable stress induced depression model rats[J].Behav Brain Res,2008,194(1):108-113.
[28]Raedler T J.Inflammatory mechanisms in major depressive disorder[J].Current Opin Psych,2011,24(6):519-525.
[29]Catenadell'Osso M,Bellantuono C,Consoli G,et al.Inflammatory and neurodegenerative pathways in depression:A new avenue for antidepressant development?[J].Current Med Chem,2011,18(2):245-255.
[30]Song C,Wang H.Cytokines mediated inflammation and decreased neurogenesis in animal models of depression[J].Progr Neuro-psychopharmacol Biol Psych,2011,35(3):760-768.
[31]Corona A W,Norden D M,Skendelas J P,et al.Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor(CX(3)CR1)-deficient mice[J].Brain Behav Imm,2013,31(24):134-142.
[32]Oxenkrug G F.Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder:The serotonin hypothesis revisited 40 years later[J].Israel J Psychiatry Relat Sci,2010,47(1):56-63.
[33]Christmas D M,Potokar J P,Davies S J.A biological pathway linking inflammation and depression:activation of indoleamine 2,3-dioxygenase[J].Neuropsych Dis Treat,2011,7(1):431-439.
[34]刘宇凝,蒋春雷,王云霞.炎症诱发抑郁症:吲哚胺2,3双加氧酶的激活是关键环节之一[J].现代生物医学进展,2012,12(14):2751-2756.
[35]Suganuma M,Okabe S,Oniyama M,et al.Wide distribution of[3H](-)-epigallocatechin gallate,a cancer preventive tea polyphenol,in mouse tissue[J].Carcinogenesis,1998,19(10):1771-1776.