NLRP3炎症小体与抑郁症的关系及中医药的干预作用

张楠; 许二平; 陈玉龙

doi:10.13422/j.cnki.syfjx.20230391

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NLRP3炎症小体与抑郁症的关系及中医药的干预作用

综述 | 更新时间：2023-01-03

- NLRP3炎症小体与抑郁症的关系及中医药的干预作用
- Relationship Between NLRP3 Inflammasome and Depression and Intervention Effect of Traditional Chinese Medicine： A Review
- 中国实验方剂学杂志 2023年29卷第3期页码：186-193
- 作者机构：
  
  河南中医药大学，郑州 450046
- 作者简介：
  
  张楠，博士，副教授，从事方剂配伍及作用机制研究， E-mail：303944828@qq.com
  许二平，教授，博士生导师，博士后合作导师，从事方剂配伍及作用机制研究，Tel：0371-65680003，E-mail：xuerping@sina.com
- 基金信息：
  
  国家自然科学基金项目(81973739);河南省高等学校青年骨干教师培养计划项目(2021GGJS087)
- DOI：10.13422/j.cnki.syfjx.20230391
  中图分类号： R2-0;R22;R285.5;R284;R749.4+1;R971+.43
- 纸质出版日期：2023-02-05，
  
  网络出版日期：2022-01-11，
  
  收稿日期：2021-10-15，
- 稿件说明：
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张楠,许二平,陈玉龙.NLRP3炎症小体与抑郁症的关系及中医药的干预作用[J].中国实验方剂学杂志,2023,29(03):186-193.

ZHANG Nan,XU Erping,CHEN Yulong.Relationship Between NLRP3 Inflammasome and Depression and Intervention Effect of Traditional Chinese Medicine： A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(03):186-193.
张楠,许二平,陈玉龙.NLRP3炎症小体与抑郁症的关系及中医药的干预作用[J].中国实验方剂学杂志,2023,29(03):186-193. DOI： 10.13422/j.cnki.syfjx.20230391.

ZHANG Nan,XU Erping,CHEN Yulong.Relationship Between NLRP3 Inflammasome and Depression and Intervention Effect of Traditional Chinese Medicine： A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(03):186-193. DOI： 10.13422/j.cnki.syfjx.20230391.

摘要

抑郁症是全球高发性精神疾病，严重威胁人们健康，带来严重的社会经济负担。近年来，随着研究的逐步深入，有关抑郁症的发病机制研究已经不再局限于神经递质、下丘脑-垂体-肾上腺轴、氧化应激等方面，神经炎症在抑郁症发病机制中的重要作用日益受到重视。研究发现，NOD样受体热蛋白结构域3（NLRP3）炎症小体作为连接心理应激和抑郁症的桥梁，可以启动炎症级联反应，介导抑郁症的产生。该文通过探讨NLRP3炎症小体与抑郁症的关系，挖掘其在抑郁症中可能存在的调控机制及作用靶点，总结中医药通过调控NLRP3炎症小体，减少炎症细胞因子释放，发挥抗抑郁的作用机制，以期为抑郁症的防治提供新的思路。

Abstract

Depression， a mental disorder with high incidence， threatens people's health and causes heavy economic burden. In recent years， the research on the pathogenesis of depression is no longer limited to neurotransmitters， hypothalamic-pituitary-adrenal axis， and oxidative stress， and neuroinflammation draws increasing attention. Studies have demonstrated that the NOD-like receptor family， pyrin domain-containing 3 （NLRP3） inflammasome as a bridge connecting psychological stress and depression can initiate inflammatory cascade to induce depression. This article expounds the relationship between NLRP3 inflammasome and depression and introduces the mechanisms and targets of NLRP3 inflammasome in regulating depression. Further， we summarize the research progress in the treatment of depression with traditional Chinese medicine， which regulates NLRP3 inflammasomes to reduce the release of inflammatory cytokines. This review is expected to provide new ideas for the prevention and treatment of depression.

关键词

NOD样受体热蛋白结构域3（NLRP3）炎症小体抑郁症中医药研究进展

Keywords

NOD-like receptor family， pyrin domain-containing 3 （NLRP3） inflammasomedepressiontraditional Chinese medicineresearch progress

references

KÖNIG H，KÖNIG H H，KONNOPKA A. The excess costs of depression：A systematic review and Meta-analysis［J］. Epidemiol Psychiatr Sci，2019，29：e30.

World Health Organization. Depression and other common mental disorders：Global health estimates［R］. Geneva：World Health Organization，2017.

HUANG Y，WANG Y，WANG H，et al. Prevalence of mental disorders in China：A cross-sectional epidemiological study［J］. Lancet Psychiatry，2019，6（3）：211-224.

程博琳，方晓艳，苗明三. 抑郁症的分子机制及中医药治疗抑郁症特点［J］. 中医学报，2014，29（2）：212-214.

SMITH R S. The macrophage theory of depression［J］. Med Hypotheses，1991，35（4）：298-306.

ZHANG H X，XU Y Q，LI Y Y，et al. Difference in proinflammatory cytokines produced by monocytes between patients with major depressive disorder and healthy controls［J］. J Affect Disord，2018，234：305-310.

KOCHAR B，BARNES E L，LONG M D，et al. Depression is associated with more aggressive inflammatory bowel disease［J］. Am J Gastroenterol，2018，113（1）：80-85.

NERURKAR L，SIEBERT S，MCINNES I B，et al. Rheumatoid arthritis and depression：An inflammatory perspective［J］. Lancet Psychiatry，2019，6（2）：164-173.

SU K P，LAI H C，PENG C Y，et al. Interferon-alpha-induced depression：Comparisons between early- and late-onset subgroups and with patients with major depressive disorder［J］. Brain Behav Immun，2019，80：512-518.

BAI S，GUO W L，FENG Y Y，et al. Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder：A systematic review and Meta-analysis of randomised controlled trials［J］. J Neurol Neurosurg Psychiatry，2020，91（1）：21-32.

ZHANG S S，ZONG Y，REN Z G，et al. Regulation of indoleamine 2，3-dioxygenase in hippocampal microglia by NLRP3 inflammasome in lipopolysaccharide-induced depressive-like behaviors［J］. Eur J Neurosci，2020，52（11）：4586-4601.

VERECZKEI A，ABDUL-RAHMAN O，HALMAI Z，et al. Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms［J］. Prog Neuropsychopharmacol Biol Psychiatry，2019，92：207-216.

WANG B，HUANG X，PAN X，et al. Minocycline prevents the depressive-like behavior through inhibiting the release of HMGB1 from microglia and neurons［J］. Brain Behav Immun，2020，88：132-143.

TSAI S J. Effects of interleukin-1beta polymorphisms on brain function and behavior in healthy and psychiatric disease conditions［J］. Cytokine Growth Factor Rev，2017，37：89-97.

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.

MAYDYCH V. The interplay between stress，inflammation，and emotional attention：Relevance for depression［J］. Front Neurosci，2019，13：384.

KAUFMANN F N，COSTA A P，GHISLENI G，et al. NLRP3 inflammasome-driven pathways in depression：Clinical and preclinical findings［J］. Brain Behav Immun，2017，64：367-383.

WONG M L，INSERRA A，LEWIS M D，et al. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition［J］. Mol Psychiatry，2016，21（6）：797-805.

MA X F，ZHU Z H，GUO S，et al. The effect of deoxyschizandrin on chronic unpredictable mild stress-induced depression［J］. Biotechnol Appl Biochem，2021，68（1）：52-59.

ZHANG Y，LIU L，LIU Y Z，et al. NLRP3 inflammasome mediates chronic mild stress-induced depression in mice via neuroinflammation［J］. Int J Neuropsychopharmacol，2015，doi：10.1093/ijnp/pyv006http://dx.doi.org/10.1093/ijnp/pyv006.

BAUERNFEIND F G，HORVATH G，STUTZ A，et al. Cutting edge：NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression［J］. J Immunol，2009，183（2）：787-791.

WANG M，YAN S G，ZHOU Y X，et al. trans-cinnamaldehyde reverses depressive-like behaviors in chronic unpredictable mild stress rats by inhibiting NF-κB/NLRP3 inflammasome pathway［J］. Evid Based Complement Alternat Med，2020，2020：4572185.

JIA K K，DING H，YU H W，et al. Huanglian-Wendan decoction inhibits NF-κB/NLRP3 inflammasome activation in liver and brain of rats exposed to chronic unpredictable mild stress［J］. Mediators Inflamm，2018，2018：3093516.

FENG X J，ZHAO Y，YANG T Y，et al. Glucocorticoid-driven NLRP3 inflammasome activation in hippocampal microglia mediates chronic stress-induced depressive-like behaviors［J］. Front Mol Neurosci，2019，12：210.

DU R W，BU W G. Metformin improves depressive-like symptoms in mice via inhibition of peripheral and central NF-κB-NLRP3 inflammation activation［J］. Exp Brain Res，2020，238（11）：2549-2556.

HUANG Z Y，TAN S J. P2X7 receptor as a potential target for major depressive disorder［J］. Curr Drug Targets，2021，22（10）：1108-1120.

IWATA M，OTA K T，LI X Y，et al. Psychological stress activates the inflammasome via release of adenosine triphosphate and stimulation of the purinergic type 2X7 receptor［J］. Biol Psychiatry，2016，80（1）：12-22.

RIBEIRO D E，RONCALHO A L，GLASER T，et al. P2X7 receptor signaling in stress and depression［J］. Int J Mol Sci，2019，20（11）：E2778.

WANG L F，NEGRO R，WU H. TRPM2，linking oxidative stress and Ca2+ permeation to NLRP3 inflammasome activation［J］. Curr Opin Immunol，2020，62：131-135.

LEE G S，SUBRAMANIAN N，KIM A I，et al. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP［J］. Nature，2012，492（7427）：123-127.

BHARTI V，TAN H，ZHOU H，et al. Txnip mediates glucocorticoid-activated NLRP3 inflammatory signaling in mouse microglia［J］. Neurochem Int，2019，131：104564.

DU R H，WU F F，LU M，et al. Uncoupling protein 2 modulation of the NLRP3 inflammasome in astrocytes and its implications in depression［J］. Redox Biol，2016，9：178-187.

丁杨，胡容. NLRP3炎症小体激活及调节机制的研究进展［J］. 药学进展，2018，42（4）：294-302.

JIA K K，PAN S M，DING H，et al. Chaihu-Shugan San inhibits inflammatory response to improve insulin signaling in liver and prefrontal cortex of CUMS rats with glucose intolerance［J］. Biomedecine Pharmacother，2018，103：1415-1428.

HAO W Z，WU J J，YUAN N J，et al. Xiaoyaosan improves antibiotic-induced depressive-like and anxiety-like behavior in mice through modulating the gut microbiota and regulating the NLRP3 inflammasome in the colon［J］. Front Pharmacol，2021，12：619103.

ZHU H Z，LIANG Y D，HAO W Z，et al. Xiaoyaosan exerts therapeutic effects on the colon of chronic restraint stress model rats via the regulation of immunoinflammatory activation induced by the TLR4/NLRP3 inflammasome signaling pathway［J］. Evid Based Complement Alternat Med，2021，2021：6673538.

JING W，SONG S S，SUN H，et al. Mahuang-Fuzi-xixin decoction reverses depression-like behavior in LPS-induced mice by regulating NLRP3 inflammasome and neurogenesis［J］. Neural Plast，2019，2019：1571392.

JIA K K，ZHENG Y J，ZHANG Y X，et al. Banxia-houpu decoction restores glucose intolerance in CUMS rats through improvement of insulin signaling and suppression of NLRP3 inflammasome activation in liver and brain［J］. J Ethnopharmacol，2017，209：219-229.

赵洪庆，唐林，吴碧茹，等. 百合地黄汤抑制NLRP3炎症小体激活改善焦虑性抑郁症模型大鼠海马神经元损伤［J］. 中国实验方剂学杂志，2021，27（20）：7-14.

尚立芝，毛梦迪，许二平，等.柴胡加龙骨牡蛎汤对抑郁大鼠海马NLRP3通路的免疫调节作用［J］.中国实验方剂学杂志，2021，27（24）：33-39.

LIU P，BAI X Y，ZHANG T，et al. The protective effect of Lonicera japonica polysaccharide on mice with depression by inhibiting NLRP3 inflammasome［J］. Ann Transl Med，2019，7（24）：811.

刘富群，高崎，王丹丹，等. 银杏酮酯对抑郁症大鼠抑郁样行为及NLRP3炎症小体的作用［J］. 上海中医药大学学报，2017，31（5）：60-65.

HUANG Q T，YE X D，WANG L J，et al. Salvianolic acid B abolished chronic mild stress-induced depression through suppressing oxidative stress and neuro-inflammation via regulating NLRP3 inflammasome activation［J］. J Food Biochem，2019，43（3）：e12742.

CHEN H F，MA Y N，CHEN M，et al. Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway［J］. Ann Palliat Med，2021，10（7）：8015-8023.

WU X L，TANG B Q，LIAO X，et al. Suppressive effects of the supercritical-carbon dioxide fluid extract of Chrysanthemum indicum on chronic unpredictable mild stress-induced depressive-like behavior in mice［J］. Food Funct，2019，10（2）：1212-1224.

LI Z F，XU H X，XU Y，et al. Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation［J］. CNS Neurosci Ther，2021，27（12）：1570-1586.

ZHANG W Y，GUO Y J，HAN W X，et al. Curcumin relieves depressive-like behaviors via inhibition of the NLRP3 inflammasome and kynurenine pathway in rats suffering from chronic unpredictable mild stress［J］. Int Immunopharmacol，2019，67：138-144.

FENG R，HE M C，LI Q，et al. Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive-like behaviors by suppressing neuroinflammation in hypothalamus of mice［J］. Phytother Res，2020，34（12）：3273-3286.

SONG Y C，SUN R X，JI Z Y，et al. Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP/TRX/NLRP3 pathway in rats［J］. Life Sci，2018，206：117-124.

XIA B M，TONG Y，XIA C B，et al. Α-cyperone confers antidepressant-like effects in mice via neuroplasticity enhancement by SIRT3/ROS mediated NLRP3 inflammasome deactivation［J］. Front Pharmacol，2020，11：577062.

TAO W W，HU Y W，CHEN Z Y，et al. Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway［J］. Phytomedicine，2021，91：153692.

XIE L L，GU Z M，LIU H Z，et al. The anti-depressive effects of hesperidin and the relative mechanisms based on the NLRP3 inflammatory signaling pathway［J］. Front Pharmacol，2020，11：1251.

ASHRAF A，MAHMOUD P A，REDA H，et al. Silymarin and silymarin nanoparticles guard against chronic unpredictable mild stress induced depressive-like behavior in mice：Involvement of neurogenesis and NLRP3 inflammasome［J］. J Psychopharmacol，2019，33（5）：615-631.

GAO H Y，ZHU X H，XI Y，et al. Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress［J］. Exp Ther Med，2018，15（2）：1574-1579.

HE M C，SHI Z，QIN M，et al. Muscone ameliorates LPS-induced depressive-like behaviors and inhibits neuroinflammation in prefrontal cortex of mice［J］. Am J Chin Med，2020，48（3）：559-577.

LIU S B，XU S L，WANG Z J，et al. Anti-depressant-like effect of sinomenine on chronic unpredictable mild stress-induced depression in a mouse model［J］. Med Sci Monit，2018，24：7646-7653.

ZHANG C Y，ZENG M J，ZHOU L P，et al. Baicalin exerts neuroprotective effects via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway in a rat model of depression［J］. Int Immunopharmacol，2018，64：175-182.

SONG M T，RUAN J，ZHANG R Y，et al. Astragaloside Ⅳ ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPARγ/NF-κB/NLRP3 inflammasome axis［J］. Acta Pharmacol Sin，2018，39（10）：1559-1570.

ZHANG L，PREVIN R，LU L，et al. Crocin，a natural product attenuates lipopolysaccharide-induced anxiety and depressive-like behaviors through suppressing NF-κB and NLRP3 signaling pathway［J］. Brain Res Bull，2018，142：352-359.

TIAN D D，WANG M，LIU A，et al. Antidepressant effect of paeoniflorin is through inhibiting pyroptosis CASP-11/GSDMD pathway［J］. Mol Neurobiol，2021，58（2）：761-776.

ZHANG Y Q，WANG X B，XUE R R，et al. Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats［J］. Neuroreport，2019，30（13）：893-900.

LI Y J，SONG W，TONG Y，et al. Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis［J］. J Neuroinflammation，2021，18（1）：1.

LI H W，LIN S Y，QIN T T，et al. Senegenin exerts anti-depression effect in mice induced by chronic un-predictable mild stress via inhibition of NF-κB regulating NLRP3 signal pathway［J］. Int Immunopharmacol，2017，53：24-32.

LIU Y M，SHEN J D，XU L P，et al. Ferulic acid inhibits neuro-inflammation in mice exposed to chronic unpredictable mild stress［J］. Int Immunopharmacol，2017，45：128-134.

GENG J，LIU J，YUAN X，et al. Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress （CUMS）-induced depressive-like behavior in mice［J］. Toxicol Appl Pharmacol，2019，379：114688.

DENG X Y，LI H Y，CHEN J J，et al. Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice［J］. Behav Brain Res，2015，291：12-19.

LIU B，XU C，WU X，et al. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation［J］. Neuroscience，2015，294：193-205.

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