NLRP3炎症小体参与Ⅱ期特发性膜性肾病发生的研究

    Participation of NLRP3 inflammasome in the pathogenesis of idiopathic membranous nephropathy

      摘要
    • 摘要: 目的 观察特发性膜性肾病（idiopathic membranous nephropathy，IMN）患者肾活检组织核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain（NOD）-like receptors family，pyrin domain containing，NLRP3），肿瘤坏死因子受体相关因子6（tumor necrosis factor receptor associated factor6，TRAF6）以及细胞外信号调节激酶（extracellular signal-regulated kinase，ERK1/2）、p38、JUN氨基末端激酶（Jun n-terminal kinase，JNK）信号通路蛋白的表达，分析尿蛋白与NLRP3以及TRAF6与NLRP3之间的相关性。方法 收集未行肾上腺皮质激素及免疫抑制剂治疗且肾活检诊断为Ⅱ期IMN患者38例，应用免疫组化方法检测各样本肾组织TRAF6、NLRP3及核因子κB（nuclear factor，NF-κB）、磷酸化ERK1/2MAPK、磷酸化p38MAPK、磷酸化JNK等因子的表达情况，并对正常组与Ⅱ期IMN患者各因子表达情况进行分析，同时收集患者的血液和24 h尿液，分析24 h尿蛋白定量、血肌酐、肌酐清除率、尿素氮等一般临床资料，对尿蛋白与NLRP3以及NLRP3与TRAF6进行相关分析。以10例因肾结核及肾肿瘤行肾切除的患者肾脏组织作为正常对照组。结果 （1）Ⅱ期IMN患者24 h尿蛋白定量、血肌酐明显高于正常组（P<0.01）；（2）Ⅱ期IMN患者肾脏中TRAF6、NLRP3蛋白表达明显高于正常组（P<0.01）；（3）24 h尿蛋白定量与NLRP3呈正相关（r=0.689，P<0.01），TRAF6与NLRP3呈正相关（r=0.490，P<0.01）；（4）NF-κB、磷酸化ERK1/2、磷酸化p38、磷酸化JNK在Ⅱ期IMN均高于正常组（P<0.01）。结论 NLRP3和TRAF6可能参与Ⅱ期IMN的发病，并与NF-κB和ERK1/2、p38、JNK信号通路的激活相关。

       

      Abstract: Objective To observe the expression of NLRP3,TRAF6,ERK1/2,p38 and JNK signaling pathway proteins in renal biopsy tissues of patients with idiopathic membranous nephropathy (IMN) and explore the correlation between urinary protein and NLRP3,TRAF6 and NLRP3.Methods From 38 IMN patients naive to adrenal corticosteroids and immunosuppressive agents,renal biopsy specimens were collected for detecting the expressions of TRAF6,NLRP3,NF-κB,phosphorylated ERK1/2MAPK,phosphorylated p38MAPK and phosphorylated JNK through immunohistochemistry.Also the levels of 24-hour urinary protein,serum creatinine,creatinine clearance and urea nitrogen were recorded.Then correlation analysis of urinary protein with NLRP3 and TRAF6.Renal tissue specimens from 10 patients undergoing nephrectomy due to renal tuberculosis or renal tumors served as normal control.Results Compared with normal group,24-hour urinary protein and serum creatinine were significantly higher in patients with stage II IMN (P<0.001).The expressions of TRAF6 and NLRP3 were significantly greater than those of normal group (P<0.0001) and the difference was statistically significant.And 24-hour urinary protein quantity was positively correlated with NLRP3 (r=0.689,P<0.01) while TRAF6 positively correlated with NLRP3 (r=0.490,P<0.01).NF-κB,phosphorylated ERK1/2,phosphorylation of p38 and phosphorylated JNK were higher than normal group (P<0.001).Conclusion Probably involved in the pathogenesis of stage II IMN,NLRP3 and TRAF6 may be associated with NF-κB and the activations of ERK1/2,p38 and JNK signaling pathways.

       

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