NLRP3炎症小体与腹膜透析患者腹膜纤维化的研究进展
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摘要
腹膜透析已逐渐成为终末期肾病患者的首选治疗方法之一,腹膜纤维化所致的超滤衰竭是患者退出腹膜透析的主要原因。Nod样受体蛋白3(NLRP3)炎症小体是一种模式识别受体,其激活可引起强效促炎因子白细胞介素(IL) 1β、IL-18的成熟和释放,在急慢性炎症反应过程及多种非感染性疾病的发生发展中发挥重要作用。NLRP3炎症小体与腹膜透析过程中的急慢性腹膜炎、腹膜纤维化的发生发展密切相关,阐明NLRP3炎症小体与腹膜透析相关腹膜纤维化的调控机制,可为腹膜纤维化的防治提供理论基础。
Peritoneal dialysis has gradually become one of the preferred treatment methods for patients with end-stage renal disease. The ultrafiltration failure caused by peritoneal fibrosis is the main reason for patients to withdraw from peritoneal dialysis. Nod-like receptor protein 3( NLRP3) inflammasome is a kind of pattern recognition receptor,and its activation can induce the maturation and release of potent proinflammatory factors interleukin( IL) 1β and IL-18,which plays an important role in the occurrence and development of acute and chronic inflammatory reactions and a variety of non-infectious diseases. In recent years,it has been found that NLRP3 inflammasome is closely related to the occurrence and development of acute and chronic peritonitis and peritoneal fibrosis in peritoneal dialysis process,so clarification of the regulatory mechanism between the NLRP3 inflammasomes and peritoneal fibrosis in peritoneal dialysis can provide a theoretical basis for the prevention and treatment of peritoneal fibrosis.
Peritoneal dialysis has gradually become one of the preferred treatment methods for patients with end-stage renal disease. The ultrafiltration failure caused by peritoneal fibrosis is the main reason for patients to withdraw from peritoneal dialysis. Nod-like receptor protein 3( NLRP3) inflammasome is a kind of pattern recognition receptor,and its activation can induce the maturation and release of potent proinflammatory factors interleukin( IL) 1β and IL-18,which plays an important role in the occurrence and development of acute and chronic inflammatory reactions and a variety of non-infectious diseases. In recent years,it has been found that NLRP3 inflammasome is closely related to the occurrence and development of acute and chronic peritonitis and peritoneal fibrosis in peritoneal dialysis process,so clarification of the regulatory mechanism between the NLRP3 inflammasomes and peritoneal fibrosis in peritoneal dialysis can provide a theoretical basis for the prevention and treatment of peritoneal fibrosis.
引文
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[13]Shi S,Zhang Y,Wen W,et al.Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells[J].Mol Med Rep,2016,14(5):4342-4348.
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[18]Chin LH,Hsu YJ,Hsu SC,et al.The regulation of NLRP3 inflammasome expression during the development of cardiac contractile dysfunction in chronic kidney disease[J].Oncotarget,2017,8(69):113303-113317.
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[28]Yao X,Carlson D,Sun Y,et al.Mitochondrial ROS induces cardiac inflammation via a pathway through mt DNA damage in a pneumoniarelated sepsis model[J].PLo S One,2015,10(10):e0139416.
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[30]Elliott EI,Sutterwala FS.Initiation and perpetuation of NLRP3inflammasome activation and assembly[J].Immunol Rev,2015,265(1):35-52.
[31]Heydrick SJ,Reed KL,Cohen PA,et al.Intraperitoneal administration of methylene blue attenuates oxidative stress,increases peritoneal fibrinolysis,and inhibits intraabdominal adhesion formation[J].J Surg Res,2007,143(2):311-319.
[32]Shah A,Xia L,Goldberg H,et al.Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH Oxidase,Nox4,in mesangial cells[J].J Biol Chem,2013,288(10):6835-6848.
[33]Hung KY,Liu SY,Yang TC,et al.High-dialysate-glucoseinduced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells[J].Oxid Med Cell Longev,2014,2014(3):642793.
[34]Heid ME,Keyel PA,Kamga C,et al.Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation[J].J Immunol,2013,191(10):5230-5238.
[35]Ding W,Guo H,Xu C,et al.Mitochondrial reactive oxygen speciesmediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury[J].Oncotarget,2016,7(14):17479-17491.
[36]Wu J,Li X,Zhu G,et al.The role of Resveratrol-induced mitophagy/autophagy in peritoneal mesothelial cells inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS[J].Exp Cell Res,2016,341(1):42-53.
[37]Granata S,Masola V,Zoratti E,et al.NLRP3 inflammasome activation in dialyzed chronic kidney disease patients[J].PLo S One,2015,10(3):e0122272.
[38]Nakahira K,Hisata S,Choi AM.The Roles of Mitochondrial DamageAssociated Molecular Patterns in Diseases[J].Antioxid Redox Signal,2015,23(17):1329-1350.
[39]Nakahira K,Haspel JA,Rathinam VA,et al.Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome[J].Nat Immunol,2011,12(3):222-230.
[40]Whitaker RM,Stallons LJ,Kneff JE,et al.Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury[J].Kidney Int,2015,88(6):1336-1344.
[41]Wei PZ,Kwan CH,Kai MC,et al.Urinary mitochondrial DNA level in non-diabetic chronic kidney diseases[J].Clin Chim Acta,2018,484:36-39.
[42]Szeto CC,Lai KB,Chow KM,et al.Plasma mitochondrial DNAlevel is a prognostic marker in peritoneal dialysis patients[J].Kidney Blood Press Res,2016,41(4):402-412.
[43]Jiang M,Wei Q,Dong G,et al.Autophagy in proximal tubules protects against acute kidney injury[J].Kidney Int,2012,82(12):1271-1283.
[44]Saitoh T,Fujita N,Jang MH,et al.Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production[J].Nature,2008,456(7219):264-268.
[45]Salminen A,Kaarniranta K,Kauppinen A.Inflammaging:Disturbed interplay between autophagy and inflammasomes[J].Aging(Albany NY),2012,4(3):166-175.
[2]Turner CM,Arulkumaran N,Singer M,et al.Is the inflammasome a potential therapeutic target in renal disease?[J].BMC Nephrol,2014,15:21.
[3]Schroder K,Tschopp J.The inflammasomes[J].Cell,2010,140(6):821-832.
[4]Rathinam VA,Vanaja SK,Fitzgerald KA.Regulation of inflammasome signaling[J].Nat Immunol,2012,13(4):333-342.
[5]Kayagaki N,Stowe IB,Lee BL,et al.Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling[J].Nature,2015,526(7575):666-671.
[6]Dubyak GR.P2X7 receptor regulation of non-classical secretion from immune effector cells[J].Cell Microbiol,2012,14(11):1697-1706.
[7]Jin C,Flavell RA.Molecular mechanism of NLRP3 inflammasome activation[J].J Clin Immunol,2010,30(5):628-631.
[8]Hautem N,Morelle J,Sow A,et al.The NLRP3 inflammasome has a critical role in peritoneal dialysis-related peritonitis[J].J Am Soc Nephrol,2017,28(7):2038-2052.
[9]Lai KN,Lai KB,Lam CW,et al.Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis[J].Am J Kidney Dis,2000,35(4):644-652.
[10]Margetts PJ,Kolb M,Yu L,et al.Inflammatory cytokines,angiogenesis,and fibrosis in the rat peritoneum[J].Am J Pathol,2002,160(6):2285-2294.
[11]Shu KH,Chuang YW,Huang ST,et al.Association of interleukin-1βgene polymorphism and peritonitis in uremic patients undergoing peritoneal dialysis[J].Blood Purif,2011,32(3):156-160.
[12]Lin CY,Roberts GW,Kift-Morgan A,et al.Pathogen-specific local immune fingerprints diagnose bacterial infection in peritoneal dialysis patients[J].J Am Soc Nephrol,2013,24(12):2002-2009.
[13]Shi S,Zhang Y,Wen W,et al.Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells[J].Mol Med Rep,2016,14(5):4342-4348.
[14]Krishnamoorthy V,Sunder S,Mahapatra HS,et al.Evaluation of Protein-Energy Wasting and Inflammation on Patients Undergoing Continuous Ambulatory Peritoneal Dialysis and its Correlations[J].Nephrourol Mon,2015,7(6):e33143.
[15]Lambie MR,Chess J,Summers AM,et al.Peritoneal inflammation precedes encapsulating peritoneal sclerosis:Results from the GLOBAL Fluid Study[J].Nephrol Dial Transplant,2016,31(3):480-486.
[16]李相友,伍军,罗丹,等.高糖腹膜透析液对人腹膜间皮细胞NLRP3-IL-1β的影响[J].北京大学学报(医学版),2017,49(6):954-960.
[17]Nold M,Goede A,Eberhardt W,et al.IL-18 initiates release of matrix metalloproteinase-9 from peripheral blood mononuclear cells without affecting tissue inhibitor of matrix metalloproteinases-1:Suppression by TNF alpha blockage and modulation by IL-10[J].Naunyn Schmiedebergs Arch Pharmacol,2003,367(1):68-75.
[18]Chin LH,Hsu YJ,Hsu SC,et al.The regulation of NLRP3 inflammasome expression during the development of cardiac contractile dysfunction in chronic kidney disease[J].Oncotarget,2017,8(69):113303-113317.
[19]Tbahriti HF,Meknassi D,Moussaoui R,et al.Inflammatory status in chronic renal failure:The role of homocysteinemia and proinflammatory cytokines[J].World J Nephrol,2013,2(2):31-37.
[20]Lai KN,Leung JC.Inflammation in peritoneal dialysis[J].Nephron Clin Pract,2010,116(1):c11-18.
[21]Williams JD,Craig KJ,Topley N,et al.Morphologic changes in the peritoneal membrane of patients with renal disease[J].J Am Soc Nephrol,2002,13(2):470-479.
[22]Strippoli R,Moreno-Vicente R,Battistelli C,et al.Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis[J].Stem Cells Int,2016,2016:3543678.
[23]Vilaysane A,Chun J,Seamone ME,et al.The NLRP3 inflammasome promotes renal inflammation and contributes to CKD[J].J Am Soc Nephrol,2010,21(10):1732-1744.
[24]Wang W,Wang X,Chun J.Inflammasome-independent NLRP3augments TGF-βsignaling in kidney epithelium[J].J Immunol,2013,190(3):1239-1249.
[25]张露.黄芪甲苷干预腹膜间皮细胞表型转化的分子机制研究[D].南京:南京中医药大学,2017.
[26]Kaser A,Blumberg RS.Survive an innate immune response through XBP1[J].Cell Res,2010,20(5):506-507.
[27]Costalonga EC,de Freitas LJ,Aragone DDSP,et al.Anti-fibrotic effects of valproic acid in experimental peritoneal fibrosis[J].PLo S One,2017,12(9):e0184302.
[28]Yao X,Carlson D,Sun Y,et al.Mitochondrial ROS induces cardiac inflammation via a pathway through mt DNA damage in a pneumoniarelated sepsis model[J].PLo S One,2015,10(10):e0139416.
[29]Shimada K,Crother TR,Karlin J,et al.Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis[J].Immunity,2012,36(3):401-414.
[30]Elliott EI,Sutterwala FS.Initiation and perpetuation of NLRP3inflammasome activation and assembly[J].Immunol Rev,2015,265(1):35-52.
[31]Heydrick SJ,Reed KL,Cohen PA,et al.Intraperitoneal administration of methylene blue attenuates oxidative stress,increases peritoneal fibrinolysis,and inhibits intraabdominal adhesion formation[J].J Surg Res,2007,143(2):311-319.
[32]Shah A,Xia L,Goldberg H,et al.Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH Oxidase,Nox4,in mesangial cells[J].J Biol Chem,2013,288(10):6835-6848.
[33]Hung KY,Liu SY,Yang TC,et al.High-dialysate-glucoseinduced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells[J].Oxid Med Cell Longev,2014,2014(3):642793.
[34]Heid ME,Keyel PA,Kamga C,et al.Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation[J].J Immunol,2013,191(10):5230-5238.
[35]Ding W,Guo H,Xu C,et al.Mitochondrial reactive oxygen speciesmediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury[J].Oncotarget,2016,7(14):17479-17491.
[36]Wu J,Li X,Zhu G,et al.The role of Resveratrol-induced mitophagy/autophagy in peritoneal mesothelial cells inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS[J].Exp Cell Res,2016,341(1):42-53.
[37]Granata S,Masola V,Zoratti E,et al.NLRP3 inflammasome activation in dialyzed chronic kidney disease patients[J].PLo S One,2015,10(3):e0122272.
[38]Nakahira K,Hisata S,Choi AM.The Roles of Mitochondrial DamageAssociated Molecular Patterns in Diseases[J].Antioxid Redox Signal,2015,23(17):1329-1350.
[39]Nakahira K,Haspel JA,Rathinam VA,et al.Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome[J].Nat Immunol,2011,12(3):222-230.
[40]Whitaker RM,Stallons LJ,Kneff JE,et al.Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury[J].Kidney Int,2015,88(6):1336-1344.
[41]Wei PZ,Kwan CH,Kai MC,et al.Urinary mitochondrial DNA level in non-diabetic chronic kidney diseases[J].Clin Chim Acta,2018,484:36-39.
[42]Szeto CC,Lai KB,Chow KM,et al.Plasma mitochondrial DNAlevel is a prognostic marker in peritoneal dialysis patients[J].Kidney Blood Press Res,2016,41(4):402-412.
[43]Jiang M,Wei Q,Dong G,et al.Autophagy in proximal tubules protects against acute kidney injury[J].Kidney Int,2012,82(12):1271-1283.
[44]Saitoh T,Fujita N,Jang MH,et al.Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production[J].Nature,2008,456(7219):264-268.
[45]Salminen A,Kaarniranta K,Kauppinen A.Inflammaging:Disturbed interplay between autophagy and inflammasomes[J].Aging(Albany NY),2012,4(3):166-175.