| 590 | 1 | 37 |
| 下载次数 | 被引频次 | 阅读次数 |
胃食管反流病(GERD)与抑郁症发病率均高,二者常共病存在,显著增加临床治疗难度,明确其共同病机是提高疗效的关键。已知食管ICC与小胶质细胞焦亡介导的炎症反应分别与GERD、抑郁症密切相关,受NLRP3炎症小体调控,但其是否介导二者焦亡而导致GERD共病抑郁仍未知。故本文旨在探索二者共病的病机本质,为其有效“异病同治”GERD共病抑郁症提高新思路及新方法,为中药复方奠定理论依据,以期提高临床疗效。
Abstract:The incidence of gastroesophageal reflux disease(GERD) and depression are both high, and the comorbidities of the two often exist, which significantly increases the difficulty of clinical treatment. Identifying the common pathogenesis is the key to improve the curative effect. It is known that esophageal ICC and microglia pyroptosis mediated inflammation are closely related to GERD and depression, respectively, and are regulated by the NLRP3 inflammatome. However, whether they mediate pyroptosis of the cells and lead to the comorbidities of GERD depression remains unknown. Therefore, the purpose of this paper is to explore the pathogenesis of the two comorbid depression, improve new ideas and new methods for the effective "co-treatment of different diseases" of GERD comorbid depression, and lay a theoretical basis for traditional Chinese medicine compound, in order to improve clinical efficacy.
1 Mittal R, Vaezi MF. Esophageal motility disorders and gastroesophageal reflux disease[J]. N Engl J Med,2020,383(20):1961-1972
2 Nirwan JS, Hasan SS, Babar ZU, et al. Global preva-lence and risk factors of gastro-oesophageal reflux dis-ease(GORD):Systematic review with meta-analysis[J]. Sci Rep, 2020,10(1):5814.
3 Lu TL, Li SR, Zhang JM, et al. Meta-analysis on the epidemiology of gastroesophageal re fl ux disease in Chi-na[J]. World J Gastroenterol, 2022, 28(45):6410-6420.
4 Marx W, Penninx B, Solmi M, et al. Major depressive disorder[J]. Nat Rev Dis Primers, 2023,9(1):44.
5 Paul S, Abbas MS, Nassar ST, et al. Correlation of anxiety and depression to the development of gastro-esophageal disease in the younger population[J]. Cure-us, 2022,14(12):e32712.
6 Chen D, Zhang Y, Huang T, et al. Depression and risk of gastrointestinal disorders:A comprehensive two-sample Mendelian randomization study of Europe-anancestry[J]. Psychol Med, 2023,53(15):7309-7321.
7 Chen G, Xie J, Ye J, et al. Depression promotes gastro-esophageal reflux disease:New evidence based on men-delian randomization[J]. Turk J Gastroenterol, 2023,34(5):457-462.
8 周金池,赵曙光,王新,等.中国部分地区基于社区人群胃食管反流病患病率Meta分析[J].胃肠病学和肝病学杂志,2020,29(9):1012-1020.Zhou JC, Zhao SG, Wang X, et al. Meta analysis of the prevalence of gastroesophageal reflux disease in commu-nity populations in some regions of China[J]. J Gastro-enterol Hepatol, 2020,29(9):1012-1020.
9 Global burden of 369 diseases and injuries in 204 coun-tries and territories, 1990-2019:A systematic analysis for the global burden of disease study 2019[J]. Lancet,2020,396(10258):1204-1222.
10 Shorey S, Ng ED, Wong C. Global prevalence of de-pression and elevated depressive symptoms among ado-lescents:A systematic review and meta-analysis[J].Br J Clin Psychol, 2022,61(2):287-305.
11 Mak A, Wu J, Chan Y, et al. Associations between gastro-oesophageal refluxDisease, generalised anxiety disorder, major depressive Eepisodes, and healthcare utilisation:A community-based study[J]. East Asian Arch Psychiatry, 2019,29(2):41-47.
12 Cookson BT, Brennan MA. Pro-inflammatory pro-grammed cell death[J]. Trends Microbiol, 2001,9(3):113 -114.
13 Friedlander AM. Macrophages are sensitive to anthrax le-thal toxin through an acid-dependent process[J]. J Biol Chem, 1986,261(16):7123-7126.
14 Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death[J]. Nature, 2015,526(7575):660-665.
15 Galluzzo L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death:Recommendations of the no-menclature committee on cell death 2018[J].Cell Death Differ, 2018,25(3):486-541.
16 Wang C, Ruan J. Mechanistic insights into gasdermin pore formation and regulation in pyroptosis[J]. J Mol Bi-ol, 2022,434(4):167297.
17 Yu P, Zhang X, Liu N, et al. Pyroptosis:Mechanisms and diseases[J]. Signal Transduct Target Ther, 2021,6(1):128.
18 Vasudevan SO, Behl B, Rathinam VA. Pyroptosis-in-duced inflammationand tissue damage[J]. Semin Immu-nol, 2023,69:101781.
19 Zhu C, Xu S, Jiang R, et al. The gasdermin family:Emerging therapeutic targets in diseases[J]. Signal Transduct Target Ther, 2024,9(1):87.
20 Huang Y, Xu W, Zhou R. NLRP3 inflammasome acti-vation and cell death[J]. Cell Mol Immunol, 2021,18(9):2114-2127.
21 Fu J, Wu H. Structural mechanisms of NLRP3 inflam-masome assembly and activation[J]. Annu Rev Immu-nol, 2023,41:301-316.
22 He Y, Hara H, Nunez G. Mechanism and regulation of NLRP3 inflammasome activation[J]. Trends Biochem Sci, 2016,41(12):1012-1021.
23 Lee BL, Stowe IB, Gupta A, et al. Caspase-11auto-proteolysis is crucial for noncanonical inflamma-some activation[J]. J Exp Med, 2018,215(9):2279-2288.
24 Zamyatina A, Heine H. Lipopolysaccharide recognition in the crossroads of TLR4 and Caspase-4/11 mediated inflammatory pathways[J]. Front Immunol, 2020,11:585146.
25 Kayagaki N, Stowe IB, Lee BL, et al. Caspase-11cleaves gasdermin D for non-canonical inflammasome sig-nalling[J]. Nature, 2015,526(7575):666-671.
26 Yang D, He Y, Munoz-planillo R, et al. Caspase-11 re-quires the pannexin-1 channel and the purinergic P2X7pore to mediate pyroptosis and endotoxicShock[J]. Im-munity, 2015,43(5):923-932.
27 Downs KP, Nguyen H, Dorfleutner A, et al. An over-view of the non-canonical inflammasome[J]. Mol As-pects Med, 2020,76:100924.
28 Foong D, Zhou J, Zarrouk A, et al. Understanding the biology of human interstitial cells of cajal in gastrointesti-nal motility[J]. Int J Mol Sci, 2020,21(12):4540.
29 Klein S, Seidler B, Kettenberger A, et al. Interstitial cells of cajal integrate excitatory and inhibitory neuro-transmission with intestinal slow-wave activity[J]. Nat Commun, 2013,4:1630.
30 Lopez-pingarron L, Almeida H, Soria-aznar M, et al.Interstitial cells of cajal and enteric nervous system in gastrointestinal and neurological pathology, relation to oxidative stress[J]. Curr Issues Mol Biol, 2023,45(4):3552-3572.
31 Friedmacher F, Rolle U. Interstitial cells of cajal:Clini-cal relevance in pediatric gastrointestinal motility disor-ders[J]. Pediatr Surg Int, 2023,39(1):188.
32 王婷,涂琴蓉,刘富林,等. Cajal间质细胞与消化系统疾病相关性研究进展[J].湖南中医杂志,2019,35(9):160 -162.Wang T, Tu QR, Liu FL, et al. Research progress on the correlation between cajal interstitial cells and diges-tive system diseases[J]. Hunan J Tradit Chin Med,2019,35(9):160-162.
33 Huizinga JD, Hussain A, Chen JH. Interstitial cells of Cajal and human colon motility in health and disease[J].Am J Physiol Gastrointest Liver Physiol, 2021,321(5):G552-G575.
34 常宗宏,邓尚新,杨娟,等. Cajal间质细胞在胃肠动力障碍性疾病中的研究[J].胃肠病学和肝病学杂志,2019,28(4):387-390.Chang ZH, Deng SX, Yang J, et al. The research of in-terstitial cells of cajal in disorders of gastrointestinal motil-ity[J]. J Gastroenterol Hepatol, 2019,28(4):387-390.
35 谭金晶,黎丽群,侯秋科,等.背俞指针疗法对GERD大鼠胃起搏区Cajal间质细胞及SCF表达的影响[J].时珍国医国药,2021,32(6):1501-1504.Tan JJ, Li LQ, Hou QK, et al. Effect of back-shu point-er therapy on the expression of cajal stromal cells and scf in gastric pacemaker area of gerd rats[J]. Lishizhen Med Mater Med Res, 2021,32(6):1501-1504.
36 李玉芳,乔大伟,顾思佳,等.六君子汤合旋覆代赭汤含药血清对大鼠胃Cajal间质细胞活性及钙离子浓度的影响[J].中医杂志,2019,60(15):6.Li YF, Qiao DW, Gu SJ, et al. Effects of liujunzi decoc-tion plus xuanfu daizhe decoction contained serum on ac-tivity and calcium concentration in rat gastric interstitial cell of cajal[J]. J Tradit Chin Med, 2019,60(15):6.
37 Kasugai K, Ogasawara N. Gastroesophageal reflux dis-ease:Pathophysiology and new treatment trends[J]. In-tern Med, 2024,63(1):1-10.
38 Ustaoglu A, Nguyen A, Spechler S, et al. Mucosal pathogenesis in gastro-esophageal reflux disease[J]. Neu-rogastroenterol Motil, 2020,32(12):e14022.
39 Wang F, Li G, Ning J, et al. Alcohol accumulation pro-motes esophagitis via pyroptosis activation[J]. Int J Biol Sci, 2018,14(10):1245-1255.
40 Zavala-solares MR, Fonseca-camarillo G, Valdovinos M, et al. Gene expression profiling of inflammatory cyto-kines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease:A cross-sectional study[J]. BMC Gastroenterol, 2021,21(1):201.
41 Yu HX, Wang XL, Zhang LN, et al. Involvement of the TLR4/NF-kappaB signaling pathway in the repair of esophageal mucosa injury in rats with gastroesophageal reflux disease[J]. Cell Physiol Biochem, 2018,51(4):1645-1657.
42 Yin XL, Wu HM, Zhang BH, et al. Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oe-sophageal epithelium irritated by acidic bile salts[J]. J Cell Mol Med, 2020,24(2):1208-1219.
43 Nadatani Y, Huo X, Zhang X, et al. NOD-Like recep-tor protein 3 inflammasome priming and activation in bar-rett′s epithelial cells[J]. Cell Mol Gastroenterol Hepa-tol, 2016,2(4):439-453.
44 Pizzagalli DA, Roberts AC. Prefrontal cortex and de-pression[J]. Neuropsychopharmacology, 2022,47(1):225 -246.
45 Borst K, Dumas AA, Prinz M. Microglia:Immune and non-immune functions[J]. Immunity, 2021,54(10):2194-2208.
46 Wu J, Li Y, Huang Y, et al. Integrating spatial and single-nucleus transcriptomic data elucidates microglial-specific responses in female cynomolgus ma-caques with depressive-like behaviors[J]. Nat Neurosci,2023,26(8):1352-1364.
47 Li B, Yang W, Ge T, et al. Stress induced microglial activation contributes to depression[J]. Pharmacol Res,2022,179:106145.
48 Xu X, Piao HN, Aosai F, et al. Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-kappaBand TNF-alpha/TNFR1/NF-kappaB pathways[J]. Br J Pharmacol, 2020,177(22):5224-5245.
49 Beurel E, Toups M, Nemeroff CB. The bidirectional re-lationship of depression and inflammation:Double trou-ble[J]. Neuron, 2020,107(2):234-256.
50 Wang H, He Y, Sun Z, et al. Microglia in depression:An overview of microglia in the pathogenesis and treat-ment of depression[J]. J Neuroinflammation, 2022,19(1):132.
51 Min X, Wang G, Cui Y, et al. Association between in-flammatory cytokines andsymptoms of major depressive disorder in adults[J]. Front Immunol, 2023,14:1110775.
52 Zhu Q, Gao Z, Peng J, et al. Lycopene alleviates chron-ic stress-induced hippocampal microglial pyroptosis by in-hibiting the cathepsin B/NLRP3 signaling pathway[J]. J Agric Food Chem, 2023,71(50):20034-20046.
53 Chai Y, Cai Y, Fu Y, et al. Salidroside ameliorates de-pression by suppressing NLRP3-mediated pyroptosis via P2X7/NF-kappaB/NLRP3 signaling pathway[J]. Front Pharmacol, 2022,13:812362.
54 Wan T, Li X, Fu M, et al. NLRP3-dependent pyropto-sis:A candidate therapeutic target for depression[J].Front Cell Neurosci, 2022,16:863426.
55 He H, Xie X, Zhang J, et al. Patchouli alcohol amelio-rates depression-like behaviors through inhibiting NL-RP3-mediated neuroinflammation in male stress-exposed mice[J]. J Affect Disord, 2023,326:120-131.
56 Alcocer-gomez E, de Miguel M, Casas-barquero N, et al. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder[J]. Brain Behav Immun, 2014,36:111-117.
57 Pandey GN, Zhang H, Sharma A, et al. Innate immuni-ty receptors in depression and suicide:Upregulated NOD-like receptors containing pyrin(NLRPs)and hy-peractive inflammasomes in the postmortem brains of people who were depressed and died by suicide[J]. J Psy-chiatry Neurosci, 2021,46(5):E538-E547.
58 Rebollo I, Tallon-baudry C. The sensory and motor components of the cortical hierarchy are coupled to the rhythm of the stomach during rest[J]. J Neurosci, 2022,42 (11):2205-2220.
59 Engelen T, Solca M, Tallon-baudry C. Interoceptive rhythms in the brain[J]. Nat Neurosci, 2023,26(10):1670-1684.
60 Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and bio-markers of integrity[J]. Fluids Barriers CNS, 2020,17(1):69.
61 Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption:Effects and mecha-nisms[J]. CNS Neurosci Ther, 2021,27(1):36-47.
62 Haruwaka K, Ikegami A, Tachibana Y, et al. Dual mi-croglia effects on blood brain barrier permeability induced by systemic inflammation[J]. Nat Commun, 2019,10(1):5816.
63 Scarpignato C, Hongo M, Wu J, et al. Pharmacologic treatment of GERD:Where we are now, and where are we going[J]. Ann N Y Acad Sci, 2020,1482(1):193 -212.
64 Thurber KM, Otto AO, Stricker SL. Proton pump in-hibitors:Understanding the associated risks and benefits of long-term use[J]. Am J Health Syst Pharm, 2023,80(8):487-494.
65 Fong P, Chan ST, Lei PN, et al. Association of suicid-al ideation and depression with the use of proton pump inhibitors in adults:A cross-sectional study[J]. Sci Rep,2022,12(1):19539.
66 汪忠镐,吴继敏,胡志伟,等.中国胃食管反流病多学科诊疗共识[J].中华胃食管反流病电子杂志,2020,7(1):1-28.Wang ZG, Wu JM, Hu ZW, et al. Consensus on multi-disciplinary diagnosis and treatment of gastroesophageal reflux disease in China[J]. Chin J Gastroesophageal Re-flux Dis(Electronic Edition), 2020,7(1):1-28.
67 Expert consensus group of integrated, Chinese ethnic medicine society mental.抑郁障碍中西医整合专家共识[J].中国医药导报,2021,18(6):4-12.Expert consensus group of integrated, et al. Expert con-sensus of integrated traditional chinese and western medi-cine for depression disorder[J]. China Med Her, 2021,18 (6):4-12.
68 何美君,贾博,白光.基于网络药理学及分子对接探讨半夏厚朴汤对胃食管反流病和抑郁症“异病同治”的作用机制[J].中医药导报,2021,27(8):138-144.He MJ, Jia B, Bai G, et al. Exploration on mechanisms of"treating different diseases with same treatment"of banxia houpo decoction in treating gastroesophageal re-flux disease and depressive disorder based on network pharmacology and molecular docking[J]. Guiding J Tra-dit Chin Med Pharm, 2021,27(8):138-144.
69 杨成宁,陈广文,黄晓燕,等.调中化湿汤治疗胃食管反流病伴焦虑抑郁患者的疗效及对血清MTL、5-HT、DA的影响[J].时珍国医国药,2021,32(4):899-902.Yang CN, Chen GW, Huang XY, et al. Therapeutic ef-fect of tiaozhonghuashi decoction on patients with gastro-esophageal reflux disease accompanied by anxiety and de-pression and its influence on serum MTL, 5-HT and DA[J]. Lishizhen Med Mater Med Res, 2021,32(0):899 -902.
70 孙叙敏,张雅月,尹璐.柴胡疏肝散合旋覆代赭汤加减治疗伴焦虑、抑郁的胃食管反流病的临床疗效[J].中国实验方剂学杂志,2021,27(8):88-93.Sun XM, Zhang YY, Yin L, et al. Clinical efficacy of modified chaihu shugansan combined with xuanfu daizhet-ang on depression of patients of patients with gastro-esophageal reflux disease[J]. Chin J Exp Tradit Med Formulae, 2021,27(8):88-93.
71 李仲贤,彭敏,徐海燕,等.调神固本整合针灸治疗轻度抑郁症共病胃食管反流病36例[J].中国针灸,2023,43 (11):1300-1302.Li ZX, Peng M, Xu HY, et al. Integrative and holistic acupuncture-moxibustion with regulating spirit and con-solidating root for 36 cases of comorbid mild depression and gastroesophageal reflux disease[J]. Chin Acupunct Moxibustion, 2023,43(11):1300-1302.
72 周晓玲,谢胜,侯秋科,等.背俞指食针疗法对GERD伴心理、睡眠障碍的治疗探讨[J].辽宁中医药大学学报,2014,16(8):106-108.Zhou XL, Xie S, Hou QK, et al. Investigation on acu-puncture therapy with finger on back-shu point for psy-chological and sleep disorders of gerd[J]. J Liaoning Univ Tradit Chin Med, 2014,16(8):106-108.
73 秦甜甜,黄如杨,谢红潇,等.基于NLRP3/细胞焦亡通路研究荆芥挥发油的抗抑郁作用及作用机制[J].中草药,2023,54(12):3878-3886.Qin TT, Huang RY, Xie HX, et al. Antidepressant ef-fect and mechanism of essential oil from schizonepeta tenuifolia based on nlrp3/pyroptosis pathway[J]. Chin Tradit Herb Drugs, 2023,54(12):3878-3886.
基本信息:
DOI:10.13210/j.cnki.jhmu.20241108.001
中图分类号:R259;R277.7
引用信息:
[1]陈南,杨成宁,王宇青,等.调控ICC-小胶质细胞焦亡交互“异病同治”GERD共病抑郁症的可行性分析[J].海南医科大学学报,2025,31(04):298-307.DOI:10.13210/j.cnki.jhmu.20241108.001.
基金信息:
广西自然科学基金项目(2024GXNSFAA999154); 国家自然科学基金资助项目(82460915、82160877、82260900); 国家中医药传承创新中心建设项目([发改办社会2022]366号); 国家中医药管理局高水平重点学科建设项目-中医养生学科(zyyzdxk-2023167)~~
2024-11-08
2024-11-08
2024-11-08