实验性IgA肾病动物模型的研究进展
|
摘要
IgA肾病(IgA Nephropathy,IgAN)为临床最常见的原发性肾小球肾炎,亚洲为该病的高发病区域。IgAN的发病机制仍未被阐述清楚,其临床治疗策略和相应的治疗药物仍有待深入研究。IgAN动物模型在IgAN病理和药物开发研究中具有重要的作用,选择一个理想的IgAN动物模型是研究者首先需解决的问题。通过查阅、整理和分析目前国内外实验性IgAN动物模型研究文献发现,当前常用的IgAN动物模型主要包括3种,即免疫诱导型、继发病变型和自发病变型。免疫诱导型中异种蛋白诱导的IgAN动物模型具有与人类IgAN患者非常相似的临床和病理学特征,为国内学者所常用;自发病变型因发病机制与人类IgAN患者发病机理类似,为国外学者所常用。
IgA nephropathy(IgAN)is the most common primary glomerulonephritis in clinic.Asia is the high incidence region of IgAN.However,the exact pathogenesis of IgAN remains unknown,and the clinical therapeutic strategies and therapeutic drugs for IgAN still need to be improved.IgAN animal models play an important role in the research of pathology and drug development of IgAN,therefore selecting a suitable IgAN animal model is critical for researchers.In this review,we summarized three types of commonly used IgAN animal models,i.e.,immuneinducing type(xenogeneic protein-induced type),secondary disease type and spontaneous disease type by reviewing the current research literatures on IgAN animal models at home and abroad.The xenogeneic proteininduced IgAN animal model was commonly used by domestic scholars because it has similar clinical and pathological features to human IgAN patients.The spontaneous disease type was commonly used by foreign scholars because its pathogenesis was similar to human IgAN patients.
IgA nephropathy(IgAN)is the most common primary glomerulonephritis in clinic.Asia is the high incidence region of IgAN.However,the exact pathogenesis of IgAN remains unknown,and the clinical therapeutic strategies and therapeutic drugs for IgAN still need to be improved.IgAN animal models play an important role in the research of pathology and drug development of IgAN,therefore selecting a suitable IgAN animal model is critical for researchers.In this review,we summarized three types of commonly used IgAN animal models,i.e.,immuneinducing type(xenogeneic protein-induced type),secondary disease type and spontaneous disease type by reviewing the current research literatures on IgAN animal models at home and abroad.The xenogeneic proteininduced IgAN animal model was commonly used by domestic scholars because it has similar clinical and pathological features to human IgAN patients.The spontaneous disease type was commonly used by foreign scholars because its pathogenesis was similar to human IgAN patients.
引文
[1]TOMINO Y,SAKAI H,MIURA M,et al.Detection of polymeric IgA in glomeruli from patients with IgA nephropathy[J].Clin Exp Immunol,1982,49(2):419-425.
[2]WYATT R J,JULIAN B A.IgA nephropathy[J].N Engl J Med,2013,368(25):2402-2414.
[3]RIFAI A,SMALL P A,TEAGUE P O,et al.Experimental IgAnephropathy[J].J Exp Med,1979,150(5):1161-1173.
[4]ISAACS K,MILLER F,LANE B.Experimental model for IgAnephropathy[J].Clin Immunol Immunopathol,1981,20(3):419-426.
[5]PESTKA J J,MOORMAN M A,WARNER R L.Dysregulation of IgA production and IgA nephropathy induced by the trichothecene vomitoxin[J].Food Chem Toxicol,1989,27(6):361-368.
[6]ZHANG Z,KUNDU G C,ZHENG F,et al.Insight into the physiological function(s)of uteroglobin by gene-knockout and antisensetransgenic approaches[J].Ann NY Acad Sci,2000,923:210-233.
[7]COPPO R.The gut-kidney axis in Ig A nephropathy:role of microbiota and diet on genetic predisposition[J].Pediatr Nephrol,2018,33(1):53-61.
[8]JIANG X,LV Y Q,ZHANG J N,et al.Mycoplasma penetrans infection is a potential cause of immunoglobulin A nephropathy:a new animal model[J].J Nephrol,2013,26(3):470-475.
[9]AMORE A,COPPO R,NEDRUD J G,et al.The role of nasal tolerance in a model of IgA nephropathy induced in mice by Sendai virus[J].Clin Immunol,2004,113(1):101-108.
[10]DAHA M R,VAN KOOTEN C.Deposition of IgA in primary IgAnephropathy:it takes at least four to tango[J].Nephrol Dial Transplant,2013,28(4):794-797.
[11]CHINTALACHARUVU S R,NAGY N U,SIGMUND N,et al.Tcell cytokines determine the severity of experimental IgAnephropathy by regulating IgA glycosylation[J].Clin Exp Immunol,2001,126(2):326-333.
[12]ZHANG Y,YAN X,ZHAO T,et al.Targeting C3a/C5a receptors inhibits human mesangial cell proliferation and alleviates immunoglobulin A nephropathy in mice[J].Clin Exp Immunol,2017,189(1):60-70.
[13]SHEN P,SHEN J,SUN C,et al.A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy[J].BMC Complement Altern Med,2016,16(1):312.
[14]SHEN P C,HE L Q.Effect of"gubentongluo formula"on the IgAclass switch recombination of B lymohocytes in peyer's patches in mice with IgA nephropathy[J].Sichuan Da Xue Xue Bao Yi Xue Ban,2016,47(3):337-341.
[15]汤颖,娄探奇,成彩联,等.实验性IgA肾病模型的改进[J].中山大学学报(医学科学版),2006,27(2):184-187.
[16]MENG T,LI X,AO X,et al.Hemolytic streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20response to the effect of Th17 cells[J].PLoS One,2014,9(9):e108723.
[17]CHEN F,MA Y L,DING H,et al.Effects of tripterygium wilfordii glycosides on regulatory T cells and Th17 in an IgAnephropathy rat model[J].Genet Mol Res,2015,14(4):14900-14907.
[18]张静,李静,桑晓红,等.运用两种BSA剂量建立IgA肾病大鼠模型观察[J].中国中西医结合肾病杂志,2013,14(1):13-16,96,97.
[19]HE L,PENG X,LIU G,et al.Anti-inflammatory effects of triptolide on IgA nephropathy in rats[J].Immunopharmacol Immunotoxicol,2015,37(5):421-427.
[20]NEWELL G C.Cirrhotic glomerulonephritis:incidence,morphology,clinical features,and pathogenesis[J].Am J Kidney Dis,1987,9(3):183-190.
[21]DOBRIN R S,KNUDSON F E,MICHAEL A F.The secretory immune system and renal disease[J].Clin Exp Immunol,1975,21(2):318-328.
[22]EMANCIPATOR S N,GALLO G R,LAMM M E.Experimental IgA nephropathy induced by oral immunization[J].J Exp Med,1983,157(2):572-582.
[23]ZOU J N,XIAO J,HU S S,et al.Toll-like receptor 4 signaling pathway in the protective effect of pioglitazone on experimental immunoglobulin a nephropathy[J].Chin Med J(Engl),2017,130(8):906-913.
[24]CHAO T K,RIFAI A,KA S M,et al.The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy[J].Kidney Int,2006,70(2):283-297.
[25]TSAI Y L,HUA K F,CHEN A,et al.NLRP3 inflammasome:pathogenic role and potential therapeutic target for IgA nephropathy[J].Sci Rep,2017,7:41123.
[26]ZHANG L,YE F,HE Y,et al.Establishment of a mouse IgAnephropathy model with the MBP-20-peptide fusion protein[J].Anat Rec(Hoboken),2010,293(10):1729-1737.
[27]HAN C,ZHANG L,ZHU X,et al.Plasma gelsolin levels are decreased and correlate with fibrosis in IgA nephropathy[J].Exp Biol Med(Maywood),2013,238(11):1318-1327.
[28]SHARMIN S,SHIMIZU Y,HAGIWARA M,et al.Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice[J].J Nephrol,2004,17(4):504-511.
[29]AMORE A,ROCCATELLO D,PICCIOTTO G,et al.Processing of IgA aggregates in a rat model of chronic liver disease[J].Clin Immunol Immunopathol,1997,84(2):107-114.
[30]WOODROFFE A J,GORMLY A A,CLARKSON A R,et al.Experimental cirrhosis and deposition of glomerular IgA immune complexes[J].Contrib Nephrol,1984,40:51-54.
[31]IMAI H,NAKAMOTO Y,ASAKURA K,et al.Spontaneous glomerular IgA deposition in ddY mice:an animal model of IgAnephritis[J].Kidney Int,1985,27(5):756-761.
[32]MUSO E,YOSHIDA H,TAKEUCHI E,et al.Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice[J].Kidney Int,1996,50(6):1946-1957.
[33]MIYAWAKI S,MUSO E,TAKEUCHI E,et al.Selective breeding for high serum IgA levels from noninbred ddY mice:isolation of a strain with an early onset of glomerular IgA deposition[J].Nephron,1997,76(2):201-207.
[34]SUZUKI H,SUZUKI Y,YAMANAKA T,et al.Genome-wide scan in a novel IgA nephropathy model identifies a susceptibility locus on murine chromosome 10,in a region syntenic to human IGAN1 on chromosome 6q22-23[J].J Am Soc Nephrol,2005,16(5):1289-1299.
[35]TOMINO Y,SHIMIZU M,KOIDE H,et al.Effect of monoclonal antibody CD4 on glomerulonephritis of ddY mice,a spontaneous animal model of IgA nephropathy[J].Am J Kidney Dis,1993,21(4):427-432.
[36]OKAZAKI K,SUZUKI Y,OTSUJI M,et al.Development of a model of early-onset Ig A nephropathy[J].J Am Soc Nephrol,2012,23(8):1364-1374.
[37]HOU S,LANDEGO I,JAYACHANDRAN N,et al.Follicular dendritic cell secreted protein FDC-SP controls IgA production[J].Mucosal Immunol,2014,7(4):948-957.
[38]XU L,LI B,HUANG M,et al.Critical role of kupffer cell CD89expression in experimental IgA nephropathy[J].PLoS One,2016,11(7):e0159426.
[39]BERTHELOT L,PAPISTA C,MACIEL T T,et al.Transglutaminase is essential for IgA nephropathy development acting through IgAreceptors[J].J Exp Med,2012,209(4):793-806.
[40]INOSHITA H,KIM BG,YAMASHITA M,et al.Disruption of Smad4expression in T cells leads to Ig A nephropathy-like manifestations[J].PLoS One,2013,8(11):e78736.
[2]WYATT R J,JULIAN B A.IgA nephropathy[J].N Engl J Med,2013,368(25):2402-2414.
[3]RIFAI A,SMALL P A,TEAGUE P O,et al.Experimental IgAnephropathy[J].J Exp Med,1979,150(5):1161-1173.
[4]ISAACS K,MILLER F,LANE B.Experimental model for IgAnephropathy[J].Clin Immunol Immunopathol,1981,20(3):419-426.
[5]PESTKA J J,MOORMAN M A,WARNER R L.Dysregulation of IgA production and IgA nephropathy induced by the trichothecene vomitoxin[J].Food Chem Toxicol,1989,27(6):361-368.
[6]ZHANG Z,KUNDU G C,ZHENG F,et al.Insight into the physiological function(s)of uteroglobin by gene-knockout and antisensetransgenic approaches[J].Ann NY Acad Sci,2000,923:210-233.
[7]COPPO R.The gut-kidney axis in Ig A nephropathy:role of microbiota and diet on genetic predisposition[J].Pediatr Nephrol,2018,33(1):53-61.
[8]JIANG X,LV Y Q,ZHANG J N,et al.Mycoplasma penetrans infection is a potential cause of immunoglobulin A nephropathy:a new animal model[J].J Nephrol,2013,26(3):470-475.
[9]AMORE A,COPPO R,NEDRUD J G,et al.The role of nasal tolerance in a model of IgA nephropathy induced in mice by Sendai virus[J].Clin Immunol,2004,113(1):101-108.
[10]DAHA M R,VAN KOOTEN C.Deposition of IgA in primary IgAnephropathy:it takes at least four to tango[J].Nephrol Dial Transplant,2013,28(4):794-797.
[11]CHINTALACHARUVU S R,NAGY N U,SIGMUND N,et al.Tcell cytokines determine the severity of experimental IgAnephropathy by regulating IgA glycosylation[J].Clin Exp Immunol,2001,126(2):326-333.
[12]ZHANG Y,YAN X,ZHAO T,et al.Targeting C3a/C5a receptors inhibits human mesangial cell proliferation and alleviates immunoglobulin A nephropathy in mice[J].Clin Exp Immunol,2017,189(1):60-70.
[13]SHEN P,SHEN J,SUN C,et al.A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy[J].BMC Complement Altern Med,2016,16(1):312.
[14]SHEN P C,HE L Q.Effect of"gubentongluo formula"on the IgAclass switch recombination of B lymohocytes in peyer's patches in mice with IgA nephropathy[J].Sichuan Da Xue Xue Bao Yi Xue Ban,2016,47(3):337-341.
[15]汤颖,娄探奇,成彩联,等.实验性IgA肾病模型的改进[J].中山大学学报(医学科学版),2006,27(2):184-187.
[16]MENG T,LI X,AO X,et al.Hemolytic streptococcus may exacerbate kidney damage in IgA nephropathy through CCL20response to the effect of Th17 cells[J].PLoS One,2014,9(9):e108723.
[17]CHEN F,MA Y L,DING H,et al.Effects of tripterygium wilfordii glycosides on regulatory T cells and Th17 in an IgAnephropathy rat model[J].Genet Mol Res,2015,14(4):14900-14907.
[18]张静,李静,桑晓红,等.运用两种BSA剂量建立IgA肾病大鼠模型观察[J].中国中西医结合肾病杂志,2013,14(1):13-16,96,97.
[19]HE L,PENG X,LIU G,et al.Anti-inflammatory effects of triptolide on IgA nephropathy in rats[J].Immunopharmacol Immunotoxicol,2015,37(5):421-427.
[20]NEWELL G C.Cirrhotic glomerulonephritis:incidence,morphology,clinical features,and pathogenesis[J].Am J Kidney Dis,1987,9(3):183-190.
[21]DOBRIN R S,KNUDSON F E,MICHAEL A F.The secretory immune system and renal disease[J].Clin Exp Immunol,1975,21(2):318-328.
[22]EMANCIPATOR S N,GALLO G R,LAMM M E.Experimental IgA nephropathy induced by oral immunization[J].J Exp Med,1983,157(2):572-582.
[23]ZOU J N,XIAO J,HU S S,et al.Toll-like receptor 4 signaling pathway in the protective effect of pioglitazone on experimental immunoglobulin a nephropathy[J].Chin Med J(Engl),2017,130(8):906-913.
[24]CHAO T K,RIFAI A,KA S M,et al.The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy[J].Kidney Int,2006,70(2):283-297.
[25]TSAI Y L,HUA K F,CHEN A,et al.NLRP3 inflammasome:pathogenic role and potential therapeutic target for IgA nephropathy[J].Sci Rep,2017,7:41123.
[26]ZHANG L,YE F,HE Y,et al.Establishment of a mouse IgAnephropathy model with the MBP-20-peptide fusion protein[J].Anat Rec(Hoboken),2010,293(10):1729-1737.
[27]HAN C,ZHANG L,ZHU X,et al.Plasma gelsolin levels are decreased and correlate with fibrosis in IgA nephropathy[J].Exp Biol Med(Maywood),2013,238(11):1318-1327.
[28]SHARMIN S,SHIMIZU Y,HAGIWARA M,et al.Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice[J].J Nephrol,2004,17(4):504-511.
[29]AMORE A,ROCCATELLO D,PICCIOTTO G,et al.Processing of IgA aggregates in a rat model of chronic liver disease[J].Clin Immunol Immunopathol,1997,84(2):107-114.
[30]WOODROFFE A J,GORMLY A A,CLARKSON A R,et al.Experimental cirrhosis and deposition of glomerular IgA immune complexes[J].Contrib Nephrol,1984,40:51-54.
[31]IMAI H,NAKAMOTO Y,ASAKURA K,et al.Spontaneous glomerular IgA deposition in ddY mice:an animal model of IgAnephritis[J].Kidney Int,1985,27(5):756-761.
[32]MUSO E,YOSHIDA H,TAKEUCHI E,et al.Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice[J].Kidney Int,1996,50(6):1946-1957.
[33]MIYAWAKI S,MUSO E,TAKEUCHI E,et al.Selective breeding for high serum IgA levels from noninbred ddY mice:isolation of a strain with an early onset of glomerular IgA deposition[J].Nephron,1997,76(2):201-207.
[34]SUZUKI H,SUZUKI Y,YAMANAKA T,et al.Genome-wide scan in a novel IgA nephropathy model identifies a susceptibility locus on murine chromosome 10,in a region syntenic to human IGAN1 on chromosome 6q22-23[J].J Am Soc Nephrol,2005,16(5):1289-1299.
[35]TOMINO Y,SHIMIZU M,KOIDE H,et al.Effect of monoclonal antibody CD4 on glomerulonephritis of ddY mice,a spontaneous animal model of IgA nephropathy[J].Am J Kidney Dis,1993,21(4):427-432.
[36]OKAZAKI K,SUZUKI Y,OTSUJI M,et al.Development of a model of early-onset Ig A nephropathy[J].J Am Soc Nephrol,2012,23(8):1364-1374.
[37]HOU S,LANDEGO I,JAYACHANDRAN N,et al.Follicular dendritic cell secreted protein FDC-SP controls IgA production[J].Mucosal Immunol,2014,7(4):948-957.
[38]XU L,LI B,HUANG M,et al.Critical role of kupffer cell CD89expression in experimental IgA nephropathy[J].PLoS One,2016,11(7):e0159426.
[39]BERTHELOT L,PAPISTA C,MACIEL T T,et al.Transglutaminase is essential for IgA nephropathy development acting through IgAreceptors[J].J Exp Med,2012,209(4):793-806.
[40]INOSHITA H,KIM BG,YAMASHITA M,et al.Disruption of Smad4expression in T cells leads to Ig A nephropathy-like manifestations[J].PLoS One,2013,8(11):e78736.