安神方颗粒对CUMS大鼠递质代谢与炎症反应的影响
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摘要
目的:探讨安神方颗粒对慢性应激抑郁模型大鼠行为学以及递质代谢和炎症反应的影响.方法:30只Wistar大鼠随机分为空白组、模型组、安神方颗粒组,每组10只;除空白组外,其余各组大鼠进行2周的慢性温和不可预知应激(CUMS)刺激;在后续3周进行CUMS 1 h前,安神方颗粒组每天给予安神方颗粒质量分数40 g/kg灌胃,空白组和模型组给予等体积生理盐水灌胃.观察各组大鼠治疗前后的体质量变化;运用强迫游泳(FST)和糖水偏好实验(SPT)评估大鼠抑郁行为的变化;通过ELISA法检测大鼠海马组织中炎症因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的含量,并通过Western blotting和免疫荧光检测大鼠海马BDNF和GABA_ARα2表达情况.结果:与空白组比较,模型组大鼠体质量增加缓慢(P <0. 01),FST累积不动时间明显延长(P <0. 01),糖水偏好值减少(P <0. 01),海马BDNF和GABA_ARα2表达水平下降(P <0. 01);与模型组比较,安神方颗粒组大鼠体质量增长较快(P <0. 01),FST累积不动时间明显缩短(P <0. 01),糖水偏好值升高(P <0. 01),海马组织中炎症因子IL-1β和TNF-α的含量降低,BDNF和GABA_ARα2表达水平上升(P <0. 01).结论:安神方颗粒可能参与干预炎症因子IL-1β和TNF-α上调海马组织BDNF和GABA_ARα2的表达,从而发挥抗抑郁的作用.
Objective: To explore the effect of Anshenfang granules( ASF) on behavior,neurotransmitter metabolism and inflammatory response in chronic stress depression model rats.Methods: Thirty Wistar rats were randomly divided into control group,model group and ASF group with10 rats in each group. Except control group,the rats of the other two group were stimulated by chronic unpredictable mild stress( CUMS) for 2 weeks. In the following 3 weeks,ASF group was intragastrically given 40 g/kg ASF at 1 h before CUMS,while control and model group were given equal volume of normal saline. The changes of body weight before and after treatment were observed. The depressive behavior of rats was assessed by forced swimming test( FST) and sugar-water preference test( SPT).The level of inflammatory factors IL-1β and TNF-α_in hippocampus of rats was detected by ELISA,and the level of BDNF and GABA_ARα-2 in hippocampus were detected by Western blotting and immunofluorescence method. Results: Compared with the control group,the weight gain of rats in the model group was slow( P < 0. 01),the accumulative immobility time of FST was significantly prolonged( P < 0. 01),the preference value of sugar and water was decreased( P < 0. 01),and the expression level of BDNF and GABA_ARα-2 in hippocampus was decreased( P < 0. 01). Compared with the model group,the weight gain of rats in ASF group was faster( P < 0. 01),the accumulative immobility time of FST was significantly shortened( P < 0. 01),the preference value of sugar and water was increased( P < 0. 01),the content of inflammatory factors IL-1β and TNF-α_in hippocampus was decreased,and the expression level of BDNF and GABA_ARα-2 was increased( P < 0. 01). Conclusion: ASF may be involved in the intervention of inflammatory factors IL-1β and TNF-α _to up-regulate the expression of BDNF and GABA_ARα-2 in hippocampus,thus playing an anti-depression role.
Objective: To explore the effect of Anshenfang granules( ASF) on behavior,neurotransmitter metabolism and inflammatory response in chronic stress depression model rats.Methods: Thirty Wistar rats were randomly divided into control group,model group and ASF group with10 rats in each group. Except control group,the rats of the other two group were stimulated by chronic unpredictable mild stress( CUMS) for 2 weeks. In the following 3 weeks,ASF group was intragastrically given 40 g/kg ASF at 1 h before CUMS,while control and model group were given equal volume of normal saline. The changes of body weight before and after treatment were observed. The depressive behavior of rats was assessed by forced swimming test( FST) and sugar-water preference test( SPT).The level of inflammatory factors IL-1β and TNF-α_in hippocampus of rats was detected by ELISA,and the level of BDNF and GABA_ARα-2 in hippocampus were detected by Western blotting and immunofluorescence method. Results: Compared with the control group,the weight gain of rats in the model group was slow( P < 0. 01),the accumulative immobility time of FST was significantly prolonged( P < 0. 01),the preference value of sugar and water was decreased( P < 0. 01),and the expression level of BDNF and GABA_ARα-2 in hippocampus was decreased( P < 0. 01). Compared with the model group,the weight gain of rats in ASF group was faster( P < 0. 01),the accumulative immobility time of FST was significantly shortened( P < 0. 01),the preference value of sugar and water was increased( P < 0. 01),the content of inflammatory factors IL-1β and TNF-α_in hippocampus was decreased,and the expression level of BDNF and GABA_ARα-2 was increased( P < 0. 01). Conclusion: ASF may be involved in the intervention of inflammatory factors IL-1β and TNF-α _to up-regulate the expression of BDNF and GABA_ARα-2 in hippocampus,thus playing an anti-depression role.
引文
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[7]黄景玉,廖潇潇,张姗红,等.抑郁症患者血清微量元素、铜蓝蛋白与执行功能的关系[J].暨南大学学报(自然科学与医学版),2017,38(5):405-410.HUANG J Y,LIAO X X,ZHANG S H,The relationship between serum trace elements, ceruloplasmin and executive function in patients with depression[J]. Journal of Jinan University(Natural Science and Medicine Edition),2017,38(5):405-410.
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[18]杜爱玲,王长虹,杨世昌.抑郁症患者血清IL-1β、IL-6水平及认知行为干预的研究[J].中国健康心理学杂志,2007,15(9):122-126.DU A L,WANG C H,YANG S C. Study on serum levels of IL-1beta and IL-6 and cognitive behavioral intervention in patients with depression[J]. Chinese Journal of Health Psychology,2007,15(9):122-126.
[19]彭云丽,王雯英,蒋春雷,等.应激诱发抑郁症的细胞因子机制研究进展[J]生理学报,2013,(2):229-236.PENG Y L,WANG W Y,JIANG C L,et al. Research progress on cytokine mechanism of stress-induced depression[J]. Journal of Physiology,2013,(2):229-236.
[20] CHHIBBER A,WOODY SK,KARIM R M,et al.Estrogen receptorβdeficiency impairs BDNF-5-HT2A signaling in the hippocampus of female brain:A possible mechanism for menopausal depression[J].Psychoneuroendocrinology,2017,6(82):107-116.
[21] XIAO J,SONG M,LI F,et al.. Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice[J]. Exp Neurol,2017,11(298):23-30.
[2] GAO S, CUI Y, YU C, et al. Tetrandrine exerts antidepressant-like effects in animal models:Role of brain-derived neurotrophic factor[J]. Behavioural Brain Research,2013,238(1):79-85.
[3] WAGER-SMITH K,MARKOU A. Depression:a repair response to stress-induced neuronal microdamage that can grade into a chronic neuroinflammatory condition?[J].Neurosci Biobehav Rev,2011,35(3):742-764.
[4] BUCKMAN A,UNDERWOOD K,CLARKE,et al. Risk factors for relapse and recurrence of depression in adults and how they operate:A four-phase systematic review and meta-synthesis[J]. Clin Psychol Rev,2018,64(8):13-38.
[5]陆惠.安神法应作为中医治疗的大法[D].广州:南方医科大学,2010:1-46.LU H. The method of tranquilizing mind should be regarded as the main method of TCM treatment[D].Guangdong:Southern Medical University,2010:1-46.
[6] SHEN J,ZHANG J,DENG M,et al. The antidepressant effect of angelica sinensis extracts on chronic unpredictable mild stress-induced depression is mediated via the upregulation of the BDNF signaling pathway in rats[J]. Evidence-Based Complementary and Alternative Medicine,2016,16(20):1-8.
[7]黄景玉,廖潇潇,张姗红,等.抑郁症患者血清微量元素、铜蓝蛋白与执行功能的关系[J].暨南大学学报(自然科学与医学版),2017,38(5):405-410.HUANG J Y,LIAO X X,ZHANG S H,The relationship between serum trace elements, ceruloplasmin and executive function in patients with depression[J]. Journal of Jinan University(Natural Science and Medicine Edition),2017,38(5):405-410.
[8]吴限亮,贾艳滨,孟宪璋.抑郁症患者述情障碍与精神症状和个性特征的相关性[J].暨南大学学报(自然科学与医学版),2013,34(2):202-206.WU X L,JIA Y B,MENG X Z. The correlation between alexithymia and psychiatric symptoms and personality characteristics in patients with depression[J]. Journal of Jinan University(Natural Science and Medicine Edition),2013,34(2):202-206.
[9] SU G Y,YANG J Y,WANG F,et al. Antidepressantlike effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress[J]. J Ethnopharmacol,2014,152(1):217-226.
[10] MICHIEL V B, JASON C,PATRICK C,et al.Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains[J]. PLo S One,2017,12(11):112-120.
[11] VOLLENWEIDER I,SMITH K S,KEIST R,et al.Antidepressant-like properties of alpha2-containing GABA(A)receptors[J]. Behav Brain Res,2011,217(1):77-80.
[12] CALETI G, ALMEIDA F B, AGNES G, et al.Antidepressant dose of taurine increases mRNA expression of GABAA receptor alpha2 subunit and BDNF in the hippocampus of diabetic rats[J]. Behav Brain Res,2015,283(2015):11-15.
[13] LUSCHER B, FUCHS T. GABAergic control of depression-related brain states[J]. Adv Pharmacol,2015,73(2015):97-144.
[14] GHOSH R,GUPTA R,BHATIA M S,et al. Comparison of efficacy,safety and brain derived neurotrophic factor(BDNF)levels in patients of major depressive disorder,treated with fluoxetine and desvenlafaxine[J]. Asian Journal of Psychiatry,2015,18(2015):37-41.
[15] PORCHER C,HATCHETT C,LONGBOTTOM R E,et al. Positive feedback regulation between gammaaminobutyric acid type A(GABA(A))receptor signaling and brain-derived neurotrophic factor(BDNF)release in developing neurons[J]. J Biol Chem,2011,286(24):21667-21677.
[16] COHEN-CORY S,KIDANE A H,SHIRKEY N J,et al.Brain-derived neurotrophic factor and the development of structural neuronal connectivity[J]. Dev Neurobiol,2010,70(5):271-288.
[17] YOU L,XIE R,HU H,et al. High levels of serumβ2-microglobulin predict severity of coronary artery disease[J]. BMC Cardiovasc Disord,2017,17(1):71-86.
[18]杜爱玲,王长虹,杨世昌.抑郁症患者血清IL-1β、IL-6水平及认知行为干预的研究[J].中国健康心理学杂志,2007,15(9):122-126.DU A L,WANG C H,YANG S C. Study on serum levels of IL-1beta and IL-6 and cognitive behavioral intervention in patients with depression[J]. Chinese Journal of Health Psychology,2007,15(9):122-126.
[19]彭云丽,王雯英,蒋春雷,等.应激诱发抑郁症的细胞因子机制研究进展[J]生理学报,2013,(2):229-236.PENG Y L,WANG W Y,JIANG C L,et al. Research progress on cytokine mechanism of stress-induced depression[J]. Journal of Physiology,2013,(2):229-236.
[20] CHHIBBER A,WOODY SK,KARIM R M,et al.Estrogen receptorβdeficiency impairs BDNF-5-HT2A signaling in the hippocampus of female brain:A possible mechanism for menopausal depression[J].Psychoneuroendocrinology,2017,6(82):107-116.
[21] XIAO J,SONG M,LI F,et al.. Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice[J]. Exp Neurol,2017,11(298):23-30.