Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress

Hui-li JIANG; Ya-xin WANG; Ya TU; Mei-hua ZENG; Jin-biao ZENG; Xiao-lan CUI; Ya-huan LI; Xing-zhou GAO; Yang SUN; Shan-shan GUO

doi:10.13422/j.cnki.syfjx.20211405

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Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress

Pharmacology | 更新时间：2021-07-15

- Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 15, Pages: 8-15(2021)
- 作者机构：
  
  1.北京中医药大学针灸推拿学院，北京 100029
  2.中国中医科学院中药研究所，北京 100700
  3.北京中医药大学国际精神疾患研究中心，北京 100029
  4.广东思济药业有限公司，广东汕头 515041
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211405
  CLC： R2-0;R22;R285.5;R33
- Received：24 March 2021，
  
  Published Online：02 June 2021，
  
  Published：05 August 2021
- 稿件说明：
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姜会梨,王雅欣,图娅等.参味宁郁片对慢性束缚应激大鼠海马TLR4/MyD88信号通路介导免疫炎症的影响[J].中国实验方剂学杂志,2021,27(15):8-15.

JIANG Hui-li,WANG Ya-xin,TU Ya,et al.Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):8-15.
姜会梨,王雅欣,图娅等.参味宁郁片对慢性束缚应激大鼠海马TLR4/MyD88信号通路介导免疫炎症的影响[J].中国实验方剂学杂志,2021,27(15):8-15. DOI： 10.13422/j.cnki.syfjx.20211405.

JIANG Hui-li,WANG Ya-xin,TU Ya,et al.Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):8-15. DOI： 10.13422/j.cnki.syfjx.20211405.

摘要

目的

探究治疗抑郁症中药新药参味宁郁片对抑郁模型大鼠行为学及海马Toll样受体4（TLR4）/髓样分化因子88（MyD88）信号通路介导免疫炎症的影响。

方法

将44只雄性SD大鼠随机分为正常组、模型组、艾司西酞普兰组和参味宁郁片组。除正常组外，其余各组大鼠均采用慢性束缚应激（CRS）结合孤养建立抑郁症模型、持续接受21 d CRS刺激；艾司西酞普兰组每日在CRS应激前1 h给予艾司西酞普兰（30 mg·kg

-1

）灌胃给药；参味宁郁片组每日在CRS应激前1 h给予参味宁郁片（18 mg·kg

-1

）灌胃干预。实验前、后通过体质量变化、糖水实验、旷场实验测试，观察各组大鼠体质量、糖水偏好指数、水平运动评分、垂直运动评分变化；采用蛋白免疫印迹法（Western blot）检测海马TLR4，MyD88蛋白表达水平，应用酶联免疫吸附测定法（ELISA）检测血清炎性因子白细胞介素-1

（IL-1

），白细胞介素-10（IL-10）和肿瘤坏死因子-

（TNF-

）含量变化。

结果

行为学结果显示，实验前，各组大鼠行为学基线水平具有一致性、各组均值差异无统计学意义。随着时间推移应激负荷增加，与正常组比较，模型组大鼠在接受CRS应激21 d后体质量、糖水偏好指数、水平运动评分和垂直运动评分均显著降低（

˂0.01），与模型组比较，参味宁郁片组和艾司西酞普兰组大鼠体质量、糖水偏好指数、水平运动评分和垂直运动评分均显著升高（

˂0.01），参味宁郁片表现出明显的抗抑郁效应；Western blot和ELISA结果显示，与正常组比较，模型组大鼠海马TLR4，MyD88蛋白及血清炎性因子IL-1

，TNF-

含量显著升高（

˂0.01），血清IL-10含量降低（

˂0.01），而与模型组比较，参味宁郁片组和艾司西酞普兰组有效逆转了应激诱导的海马TLR4，MyD88蛋白及血清炎性因子IL-1

含量显著升高、血清IL-10含量降低情况，差异具有统计学意义（

˂0.01）。

结论

治疗抑郁症中药新药参味宁郁片对慢性应激诱导抑郁症的抗抑郁作用可能是通过抑制海马TLR4/MyD88信号通路介导的免疫炎性反应途径有关。

Abstract

Objective

To explore the effects of Shenwei Ningyu pills （SNP）， a new Chinese medicine for depression， on the immunoinflammatory response mediated by Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88） signaling pathway in the hippocampus of rats exposed to chronic restraint stress （CRS）.

Method

Forty-four male Sprague Dawley rats were randomly enrolled into a normal group， a model group， an escitalopram group， and an SNP group. Except for the rats in the normal group， all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram （30 mg·kg

-1

） and SNP （18 mg·kg

-1

） one hour prior to CRS， respectively. The changes in body weight， sucrose preference index， horizontal movement scores， and vertical movement scores were observed by body weight assessment， sucrose preference test， and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1

（IL-1

）， IL-10， and tumor necrosis factor-

（TNF-

） was detected by enzyme-linked immunosorbent assay （ELISA）.

Result

The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However， significant differences were found among the groups following different interventions. The body weight， sugar preference index， horizontal movement score， and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group （

0.01）. The above indicators in the SNP

group and the escitalopram group were higher than those in the model group （

0.01）， which indicated that SNP

exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group， the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1

and TNF-

（

˂0.01） and dwindled serum IL-10 （

˂0.01）， while SNP

and escitalopram reversed the conditions in the model group （

˂0.01） except for TNF-

Conclusion

The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.

关键词

Keywords

references

SINGH J B ， DALY E J ， MATHEWS M ， et al . Approval of esketamine for treatment-resistant depression ［J］. Lancet Psychiatry ， 2020 ， 7 （ 3 ）： 232 - 235 .

FERRARI A J ， SOMERVILLE A J ， BAXTER A J ， et al . Global variation in the prevalence and incidence of major depressive disorder： a systematic review of the epidemiological literature ［J］. Psychol Med ， 2013 ， 43 （ 3 ）： 471 - 481 .

CHARLSON F J ， FERRARI A J ， FLAXMAN A D ， et al . The epidemiological modelling of dysthymia： application for the Global Burden of Disease Study 2010 ［J］. J Affect Disord ， 2013 ， 151 （ 1 ）： 111 - 120 .

American Psychiatric Association （APA） . Diagnostic and statistical manual of mental disorders ［M］. 4 th ed . Washington ： American Psychiatric Association ， 1994 .

WHITEFORD H A ， DEGENHARDT L ， REHM J ， et al . Global burden of disease attributable to mental and substance use disorders：findings from the Global Burden of Disease Study 2010 ［J］. Lancet ， 2013 ， 382 （ 9904 ）： 1575 - 1586 .

BRADFORD H ， HIDEYUKI N ， SUN Z J ， et al . Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database ［J］. PLoS One ， 2013 ， 8 （ 10 ）： 65 .

BRAMBILLA P ， CIPRIANI A ， HOTOPF M ， et al . Side-effect profile of fluoxetine in comparison with other SSRIs，tricyclic and newer antidepressants： a Meta-analysis of clinical trial data ［J］. Pharmacopsychiatry ， 2005 ， 38 （ 2 ）： 69 - 77 .

THASE M E . Preventing relapse and recurrence of depression： a brief review of therapeutic options ［J］. CNS Spectr ， 2006 ， 11 （12 Suppl 15 ）： 12 - 21 .

UHER R.Genes ， environment ， and individual differences in responding to treatment for depression ［J］. Harv Rev Psychiatry ， 2011 ， 19 （ 3 ）： 109 - 124 .

GOMEZ F ， VENERO C ， VIVEROS M P ， et al . Short-term fluoxetine treatment induces neuroendocrine and behavioral anxiogenic-like responses in adolescent male rats ［J］. Exp Brain Res ， 2015 ， 233 （ 3 ）： 983 - 995 .

KÉRI S ， SZABÓ C ， KELEMEN O . Expression of Toll-like receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder ［J］. Brain Behav Immun ， 2014 ， 40 ： 235 - 243 .

HINES D J ， CHOI H B ， HINES R M ， et al . Prevention of LPS-induced microglia activation，cytokine production and sickness behavior with TLR4 receptor interfering peptides ［J］. PLoS One ， 2013 ， 8 （ 3 ）： e60388 .

DANTZER R ， KELLEY K W . Twenty years of research on cytokine-induced sickness behavior ［J］. Brain Behav Immun ， 2007 ， 21 （ 2 ）： 153 - 160 .

DANTZER R . Cytokine-induced sickness behaviour：a neuroimmune response to activation of innate immunity ［J］. Eur J Pharmacol ， 2004 ， 500 （ 1/3 ）： 399 - 411 .

MILLER A H ， MALETIC V ， RAISON C L . Inflammation and its discontents：the role of cytokines in the pathophysiology of major depression ［J］. Biol Psychiatry ， 2009 ， 65 （ 9 ）： 732 - 741 .

PANDEY G N ， RIZAVI H S ， REN X ， et al . Toll-like receptors in the depressed and suicide brain ［J］. J Psychiatr Res ， 2014 ， 53 ： 62 - 68 .

SCHNEIDER B ， PHILIPP M ， MÜLLER M J . Psychopathological predictors of suicide in patients with major depression during a 5-year follow-up ［J］. Eur Psychiatry ， 2001 ， 16 （ 5 ）： 283 - 288 .

图娅 . 一种抗抑郁症的中药组合物及其制备方法：中国， CN1579461 ［P］. 2005-02-16 .

WANG Y ， JIANG H ， MENG H ， et al . Genome-wide transcriptome analysis of hippocampus in rats indicated that TLR/NLR signaling pathway was involved in the pathogenisis of depressive disorder induced by chronic restraint stress ［J］. Brain Res Bull ， 2017 ， 134 ： 195 - 204 .

HINWOOD M ， MORANDINI J ， DAY T A ， et al . Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex ［J］. Cereb Cortex ， 2012 ， 22 （ 6 ）： 1442 - 1454 .

EDWARDS J G ， ANDERSON I . Systematic review and guide to selection of selective serotonin reuptake inhibitors ［J］. Drugs ， 1999 ， 57 （ 4 ）： 507 - 533 .

NI J W ， MATSUMOTO K ， LI H B ， et al . Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat ［J］. Brain Res ， 1995 ， 673 （ 2 ）： 290 - 296 .

MCEWEN B S . Protective and damaging effects of stress mediators ［J］. N Engl J Med ， 1998 ， 338 （ 3 ）： 171 - 179 .

IWATA M ， OTA K T ， DUMAN R S . The inflammasome：pathways linking psychological stress，depression，and systemic illnesses ［J］. Brain Behav Immun ， 2013 ， 31 ： 105 - 114 .

BOSANAC P ， CASTLE D . How should we manage anxiety in patients with schizophrenia？［J］. Australas Psychiatry ， 2015 ， 23 （ 4 ）： 374 - 377 .

ABRAM K M ， ZWECKER N A ， WELTY L J ， et al . Comorbidity and continuity of psychiatric disorders in youth after detention： a prospective longitudinal study ［J］. JAMA Psychiatry ， 2015 ， 72 （ 1 ）： 84 - 93 .

苏晓鹏，孙文军，张潞潞，等 . 基于阳气的重要性从五脏阳气论治抑郁症——国家名老中医唐启盛教授神志病学术思想系列之一［J］. 世界中医药， 2019 ， 14 （ 12 ）： 3302 - 3305 .

CAPURON L ， PAGNONI G ， DRAKE D F ， et al . Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration ［J］. Arch Gen Psychiatry ， 2012 ， 69 （ 10 ）： 1044 - 1053 .

EISENBERGER N I ， BERKMAN E T ， INAGAKI T K ， et al . Inflammation-induced anhedonia： endotoxin reduces ventral striatum responses to reward ［J］. Biol Psychiatry ， 2010 ， 68 （ 8 ）： 748 - 754 .

FELGER J C ， MUN J ， KIMMEL H L ， et al . Chronic interferon- α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates ［J］. Neuropsychopharmacology ， 2013 ， 38 （ 11 ）： 2179 - 2187 .

DOWELL N G ， COOPER E A ， TIBBLE J ， et al . Acute changes in striatal microstructure predict the development of interferon-alpha induced fatigue ［J］. Biol Psychiatry ， 2016 ， 79 （ 4 ）： 320 - 328 .

HARRISON N A ， CERCIGNANI M ， VOON V ， et al . Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants ［J］. Neuropsychopharmacology ， 2015 ， 40 （ 4 ）： 831 - 838 .

BIRAGYN A ， RUFFINI P A ， LEIFER C A ， et al . Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2 ［J］. Science ， 2002 ， 298 （ 5595 ）： 1025 - 1029 .

FLESHNER M ， FRANK M ， MAIER S F . Danger signals and inflammasomes：stress-evoked sterile inflammation in mood disorders ［J］. Neuropsychopharmacology ， 2017 ， 42 （ 1 ）： 36 - 45 .

YANG J ， LIU R ， LU F ， et al . Fast green FCF attenuates lipopolysaccharide-induced depressive-like behavior and downregulates TLR4/Myd88/NF- κ B signal pathway in the mouse hippocampus ［J］. Front Pharmacol ， 2019 ， 10 ： 501 .

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