MCP-1、TLR-4及尿蛋白定量与原发性IgA肾病病理损伤的相关性研究
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摘要
目的探讨原发性Ig A肾病(Ig A nephropathy,Ig AN)肾组织中单核细胞趋化蛋白-1(MCP-1)、Toll样受体4(TLR-4)表达及24 h尿蛋白定量水平,分析其与肾脏损伤程度的相关性。方法选择2015年1月—2017年8月收治的67例原发性Ig AN患者。所有患者取肾活检标本,采用免疫组化法测定肾组织中MCP-1与TLR-4的表达,采用免疫比浊法测定24 h尿蛋白定量。比较不同Lee分级和肾小管间质损伤分级患者间MCP-1、TLR-4表达及24 h尿蛋白定量水平,并进一步分析MCP-1、TLR-4表达与24 h尿蛋白定量间的相关性。结果原发性Ig AN患者MCP-1及24 h尿蛋白定量水平随着Lee病理分级和肾小管间质损伤程度的加重均有升高趋势(P <0. 01),而不同Lee分级和肾小管间质损伤分级原发性Ig AN患者TLR-4表达水平比较差异无统计学意义(P> 0. 05)。原发性Ig AN肾组织中MCP-1、TLR-4表达与24 h尿蛋白定量呈正相关(r=0. 5 281、0. 6 262,P <0. 01)。结论 MCP-1与原发性Ig AN存在密切关系,其表达可作为判断原发性Ig AN病变程度的重要指标;尿蛋白是Ig AN进展及预后的危险因素。
Objective To investigate correlations between monocyte chemotactic protein-1( MCP-1) and Toll like receptor 4( TLR-4) expressions and level of urine protein quantitation within 24 h in renal tissues of patients with primary Ig A nephropathy( Ig AN) with degree of renal injury. Methods Renal biopsy specimens were taken from 67 patients with primary Ig AN admitted during January 2015 and August 2017. Expressions of MCP-1 and TLR-4 in renal tissues were detected by immunohistochemistry method,and urine protein quantitation within 24 h was detected by immunoturbidimetry. MCP-1 and TLR-4 expressions and urine protein quantitation within 24 h were compared among patients with different Lee classification and kidney tubules mesenchymal injury,and correlations between MCP-1 and TLR-4 expressions with urine protein quantitation within 24 h were further analyzed. Results Levels of MCP-1 and urine protein quantitation within 24 h in patients with primary Ig AN were increased with aggravation of Lee pathological grades and degrees of kidney tubules of mesenchymal injury( P < 0. 01). There were no significant differences in TLR-4 expressions among primary Ig AN patients with different Lee grades and degrees of kidney tubules of mesenchymal injury( P > 0. 05).MCP-1 and TLR-4 expressions were positively correlated with urine protein quantitation within 24 h in primary Ig AN renal tissues( r = 0. 5 281,0. 6 262,P < 0. 01). Conclusion MCP-1 has a close correlation with primary Ig AN,and its expression can be used as judging degree of renal pathological changes in primary Ig AN renal tissues. Urinary protein is a risk factor for progression and prognosis of Ig AN.
Objective To investigate correlations between monocyte chemotactic protein-1( MCP-1) and Toll like receptor 4( TLR-4) expressions and level of urine protein quantitation within 24 h in renal tissues of patients with primary Ig A nephropathy( Ig AN) with degree of renal injury. Methods Renal biopsy specimens were taken from 67 patients with primary Ig AN admitted during January 2015 and August 2017. Expressions of MCP-1 and TLR-4 in renal tissues were detected by immunohistochemistry method,and urine protein quantitation within 24 h was detected by immunoturbidimetry. MCP-1 and TLR-4 expressions and urine protein quantitation within 24 h were compared among patients with different Lee classification and kidney tubules mesenchymal injury,and correlations between MCP-1 and TLR-4 expressions with urine protein quantitation within 24 h were further analyzed. Results Levels of MCP-1 and urine protein quantitation within 24 h in patients with primary Ig AN were increased with aggravation of Lee pathological grades and degrees of kidney tubules of mesenchymal injury( P < 0. 01). There were no significant differences in TLR-4 expressions among primary Ig AN patients with different Lee grades and degrees of kidney tubules of mesenchymal injury( P > 0. 05).MCP-1 and TLR-4 expressions were positively correlated with urine protein quantitation within 24 h in primary Ig AN renal tissues( r = 0. 5 281,0. 6 262,P < 0. 01). Conclusion MCP-1 has a close correlation with primary Ig AN,and its expression can be used as judging degree of renal pathological changes in primary Ig AN renal tissues. Urinary protein is a risk factor for progression and prognosis of Ig AN.
引文
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[19] Grandaliano G,Gesualdo L,Ranieri E,et al. Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides:a pathogenetic role in interstitial monocytes recruitment[J]. J Am Soc Nephrol,1996,7(6):906-913.
[20]张国珍,吴小川,彭小杰,等.黄芪对实验性Ig A肾病大鼠肾小管间质损害及NF-κB MCP-1表达的影响[J].中国当代儿科杂志,2008,10(2):173-178.
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[2] Suzuki H. Ig A nephropath[J]. Nihon Jinzo Gakkai Shi,2015,57(8):1349-1353.
[3] Lai K N. Pathogenesis of IGA nephropathy[J]. Nat Rev Nephrol,2012,8(5):275-283.
[4] Gharavi A G,Kiryluk K,Choi M,et al. Genome-wide association study identifies susceptibility loci for iga nephropathy[J]. Nat Genet,2011,43(4):321-327.
[5] Han S H,Kang E W,Kie J H,et al. spontaneous remission of iga nephropathy associated with resolution of hepatitis a[J]. Am J Kidney Dis,2010,56(6):1163-1167.
[6] Novak J,Julian B A,Mestecky J,et al. Glycosylation of iga1 and pathogenesis of iga nephropathy[J]. Semin Immunopathol,2012,34(3):365-382.
[7] Aleyd E,Al M,Tuk C W,et al. Ig A Complexes in Plasma and Synovial Fluid of Patients with Rheumatoid Arthritis Induce Neutrophil Extracellular Traps via FcalphaRI[J]. J Immunol,2016,197(12):4552-4559.
[8] Floege J,Eitner F. Current therapy for iga nephropathy[J]. J Am Soc Nephrol,2011,22(10):1785-1794.
[9] Vuong M T,Hahn-Zoric M,Lundberg S,et al. Association of soluble CD89 levels with disease progression but not susceptibility in IGA nephropathy[J]. Kidney Int,2010,78(12):1281-1287.
[10] Farris A B,Colvin R B. Renal interstitial fibrosis:mechanisms and evaluation[J]. Curr Opin Nephrol Hypertens,2012,21(3):289-300.
[11] Jabur W L. Necrotic crescentic glomerulonephritis and IGA nephropathy:Lee-Haas classification revisited[J].Saudi J Kidney Dis Transpl,2011,22(4):784-787.
[12] Katafuchi R,Kiyoshi Y,Oh Y,et al. Glomerular score as a prognosticator in iga nephropathy:its usefulness and limitation[J]. Clin Nephrol,1998,49(1):1-8.
[13] Yeo S C,Liew A,Barratt J. Emerging therapies in immunoglobulin A nephropathy[J]. Nephrology(Carlton),2015,20(11):788-800.
[14] El Karoui K,Hill G S,Karras A,et al. A clinicopathologic study of thrombotic microangiopathy in iga nephropathy[J]. J Am Soc Nephrol,2012,23(1):137-148.
[15] Strutz F,Neilson E G. New insights into mechanisms of fibrosis in immune renal injury[J]. Springer Semin Immunopathol,2003,24(4):459-476.
[16]孙阳,赵艳红,卢永新,等.肾脏纤维化的发病机制及治疗进展[J].实用临床医药杂志,2015,19(9):173-176.
[17] Dunning A M,Ellis P D,McBride S,et al. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer[J]. Cancer Res,2003,63(10):2610-2615.
[18] Kuki K,Gotoh H,Hayashi M,et al. Immunity of tonsil and iga nephropathy--relationship between iga nephropathy and tonsillitis[J]. Acta Otolaryngol Suppl,2004,555:6-9.
[19] Grandaliano G,Gesualdo L,Ranieri E,et al. Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides:a pathogenetic role in interstitial monocytes recruitment[J]. J Am Soc Nephrol,1996,7(6):906-913.
[20]张国珍,吴小川,彭小杰,等.黄芪对实验性Ig A肾病大鼠肾小管间质损害及NF-κB MCP-1表达的影响[J].中国当代儿科杂志,2008,10(2):173-178.
[21] Banas M C,Banas B,Hudkins K L,et al. TLR-4 links podocytes with the innate immune system to mediate glomerular injury[J]. J Am Soc Nephrol,2008,19(4):704-713.
[22] Leemans J C,Stokman G,Claessen N,et al. Renal-assoeiated TLR2 mediates isehemia/reperfusion injury in the kidney[J]. Clin Invest,2005,115(10):2894-2903.
[23] Motojima M,Matsusaka T,Kon V,et al. Fibrinogen that appears in bowman's space of proteinuric kidneys in vivo activates podocyte toll-like receptors 2 and 4 in vitro[J].Nephron Exp Nephrol,2010,114(2):e39-47.