痛风急性和慢性期分子机制研究进展
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摘要
痛风是嘌呤代谢紊乱的代谢性疾病,其发病率呈明显升高趋势发展。痛风分为无症状的高尿酸血症时期、急性痛风关节炎时期、间歇期、慢性痛风关节炎时期。痛风急性期以激活TOLL样受体(TLRs)、NOD样受体蛋白3(NLRP3)、P2X7受体(P2X7R)为主;痛风慢性期以刺激中性粒细胞胞外诱捕网(NETs)生成、内质网应激,激活核转录因子-κB受体(RANK)为主。作者对痛风急性、慢性期分子机制进行综述,为开展中医药治疗痛风的药理机制研究,研发治疗痛风中药提供参考。
Gout is a metabolic disease with metabolic disorders of purine,and its incidence is obviously increasing.Course of gout is divided into asymptomatic period of hyperuricemia,acute gout arthritis,intermittent,and chronicgout arthritis. The acute phase of gout activates TOLL-like receptors(TLRs), NOD-like receptor protein 3(NLRP3), and P2X7 receptor(P2X7R); the chronic phase of gout stimulates neutrophil extracellular trappingnetworks(NETs) generation,endoplasmic reticulum stress,activation of nuclear transcription factor-κB receptor(RANK). This article reviews the molecular mechanisms of acute and chronic gout,and provides references for theresearch of pharmacological mechanisms of gout and the development of traditional Chinese medicine for treating gout.
Gout is a metabolic disease with metabolic disorders of purine,and its incidence is obviously increasing.Course of gout is divided into asymptomatic period of hyperuricemia,acute gout arthritis,intermittent,and chronicgout arthritis. The acute phase of gout activates TOLL-like receptors(TLRs), NOD-like receptor protein 3(NLRP3), and P2X7 receptor(P2X7R); the chronic phase of gout stimulates neutrophil extracellular trappingnetworks(NETs) generation,endoplasmic reticulum stress,activation of nuclear transcription factor-κB receptor(RANK). This article reviews the molecular mechanisms of acute and chronic gout,and provides references for theresearch of pharmacological mechanisms of gout and the development of traditional Chinese medicine for treating gout.
引文
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[4]CHEN Y,TANG Z,HUANG Z,et al.The prevalence of gout in mainland China from 2000 to 2016:a systematic review and metaanalysis[J].Journal of Public Health,2017,25(5):521-529.
[5]那莎,段陈方圆,王璐,等.牛膝总皂苷对大鼠急性痛风性关节炎的防治作用及机制研究[J].中国临床药理学与治疗学,2017,22(9):966-971.
[6]李钟,韩彬,黄惠珠,等.虎杖-桂枝药对配伍对急性痛风性关节炎大鼠TLR4/MyD88信号转导通路的影响[J].广州中医药大学学报,2015,32(6):1040-1046.
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[10]TANG A C,RAHAVI S M,FUNG S Y,et al.Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1βproduction[J].Cell Death&Disease,2018,9(2):162-174.
[11]LIU S,JIA H,HOU S,et al.Recombinant Mtb9.8 of Mycobacterium bovis stimulates TNF-αand IL-1βsecretion by RAW264.7macrophages through activation of NF-κB pathway via TLR2[J].Scientific Reports,2018,8(1):1928-1938.
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[13]SRIVASTAVA N,SHELLY A,KUMAR M,et al.Aeromonas hydrophila utilizes TLR4 topology for synchronous activation of MyD88 and TRIF to orchestrate anti-inflammatory responses in zebrafish[J].Cell Death Discov,2017,3:17067-17075.
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[18]LIU J,QIAN C,CAO X.Post-translational modification control of innate immunity[J].Immunity,2016,45(1):15-30.
[19]MóTYáN J A,BAGOSSI P,BENK S,et al.A molecular model of the full-length human NOD-like receptor family CARD domain containing 5(NLRC5)protein[J].Bmc Bioinformatics,2013,14(1):275-285.
[20]SUE F,KOGA K,TAGUCHI A,et al.Effects of omega-3 fatty acids on Nod-like receptor 3(NLRP3)inflammasome in decidualmacrophages[J].Journal of Reproductive Immunology,2016,115:33-33.
[21]HO S C,CHANG Y H.Comparison of inhibitory capacities of 6-,8-and 10-gingerols/shogaols on the canonical NLRP3 inflammasomemediated IL-1βSecretion[J].Molecules,2018,23(2):466-477.
[22]CAO W,YAN Z,SU S,et al.Chlamydial plasmid-encoded protein pORF5 induces production of IL-1βand IL-18 via NALP3inflammasome activation and p38 MAPK pathway[J].Int J Clin Exp Med,2015,8(11):20368-20379.
[23]LIU H J,PAN X X,LIU B Q,et al.Grape seed-derived procyanidins alleviate gout pain via NLRP3 inflammasome suppression[J].Journal of Neuroinflammation,2017,14(1):74-74.
[24]SCHORN C,FREY B,LAUBER K,et al.Sodium overload and water influx activate the NALP3 inflammasome[J].Journal of Biological Chemistry,2011,286(1):35-41.
[25]ABAIS J M,XIA M,ZHANG Y,et al.Redox regulation of NLRP3 inflammasomes:ROS as trigger or effector[J].Antioxidants&Redox Signaling,2015,22(13):1111-1129.
[26]林椠.痛风康宁方对急性痛风性关节炎大鼠血清症因子及氧化应激的影响[D].唐山:华北理工大学,2018.
[27]ANDRéS M,FRANCéS R,PASCUAL E.Uric acid enhances monosodium urate induced pro-inflammatory response in gouty patients:A basic and translational research study[J].Annals of the Rheumaic Diseases,2015,74(Suppl 2):777-778.
[28]GREEN J P,SOUILHOL C,XANTHIS I,et al.Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38signalling[J].Cardiovascular Research,2017,114(2):324-335.
[29]GONG Q Y,CHEN Y.Correlation between P2X7 receptor gene polymorphisms and gout[J].Rheumatology International,2015,35(8):1307-1310.
[30]RABADI M M,KIM M,LI H,et al.ATP induces PAD4 in renal proximal tubule cells via P2X7 receptor activation to exacerbate ischemic AKI[J].Am J Physiol Renal Physiol,2018,314(2):293-305.
[31]GIULIANI A L,SARTI A C,FALZONI S,et al.The P2X7receptor-interleukin-1 liaison[J].Front Pharmacol,2017,8:123-132.
[32]STOKES L,FULLER S J,SLUYTER R,et al.Two haplotypes of the P2X(7)receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion[J].Faseb Journal,2010,24(8):2916-2927.
[33]DE T C,BARBERà-CREMADES M,GóMEZ A I,et al.Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process[J].Sci Rep,2016,6:22586-22596.
[34]MARTINON F,PéTRILLIV V,MAYOR A,et al.Gout-associated uric acid crystals activate the NALP3 inflammasome[J].Nature,2006,440:237-247.
[35]MARTINON F,PéTRILLI V,MAYOR A,et al.Gout-associated uric acid crystals activate the NALP3 inflammasome[J].Nature,2006,440:237-241.
[36]KUMAGAI Y,AKIRA S.Role of TLR-dependent and independent pathways in autoimmunity[J].Nihon Rinsho Japanese Journal of Clinical Medicine,2009,67(3):487-493.
[37]MITROULIS I,KAMBAS K,CHRYSANTHOPOULOU A,et al.Neutrophil extracellular trap formation is associated with IL-1βand autophagy-related signaling in gout[J].Plos One,2011,6(12):e29318.
[38]SCHAUER C,JANKO C,MUNOZ L E,et al.Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines[J].Nature Medicine,2014,20(5):511-517.
[39]SCHETT G,SCHAUER C,HOFFMANN M,et al.Review:Why does the gout attack stop?A roadmap for the immune pathogenesis of gout[J].Rmd Open,2015,1(Suppl 1):e000046.
[40]PANG L,HAYES C P,BUAC K,et al.Pseudogout-associated inflammatory calcium pyrophosphate dihydrate microcrystals induce formation of neutrophil extracellular traps[J].Journal of Immunology,2013,190(12):6488-6500.
[41]NAKAMURA S,MIKI H,KIDO S,et al.Activating transcription factor 4,an ER stress mediator,is required for,but excessive ERstress suppresses osteoblastogenesis by bortezomib[J].International Journal of Hematology,2013,98(1):66-73.
[42]LEE H Y,CHAE H J,PARK S Y,et al.Porcine placenta hydrolysates enhance osteoblast differentiation through their antioxidant activity and effects on ER stress[J].Bmc Complementary&Alternative Medicine,2016,16(1):291-300.
[43]TANAKA K,KAJI H,YAMAGUCHI T,et al.Involvement of the osteoinductive factors,Tmem119 and BMP-2,and the ER stress response PERK-eIF2α-ATF4 pathway in the commitment of myoblastic into osteoblastic cells[J].Calcif Tissue Int,2014,94(4):454-464.
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