目的:探讨IgA肾病(IgAN)患者血清microRNA-200家族(miR-200a、miR-200b、miR-200c、miR-141、miR-429)表达及其与临床、病理及预后等指标的相关关系,进而探讨血清miR-200家族作为反映IgAN进展及预后的生物学标志物可行性.方法:收集新发33例IgA肾病患者血清标本(IgAN组),来自于15例健康志愿者血清(健康对照组),用荧光实时定量PCR行血清miR-200家族检测,比较两组间其表达差异性及相关性.结果:与对照组相比,IgAN组血清miR-200a、miR-141、miR-429表达上调(P＜0.05).IgAN患者血清miR-200b、miR-141、miR-429表达与尿蛋白水平(r=0.413,P=0.021;r =0.452,P=0.014;r =0.370,P=0.040)呈正相关关系;血清miR-200b、miR-200c、miR-141、miR-429表达与eGFR呈负相关关系(r=-0.403,P=0.020;r=-0.517,P=0.002;r=-0.398,P=0.024;r=-0.350,P=0.046);血清miR-200a、miR-200c、miR-429与血尿程度呈正相关(r=0.361,P=0.036;r=0.367,P=0.033;r=0.397,P=0.020);血清miR-200b、miR-429与肾小球硬化程度呈正相关(r=0.377,P=0.034;r =0.335,P =0.047).IgAN血清miR-200a、miR-200b、miR-200c、miR-141、miR-429之间呈明显正相关关系(P ＜0.001).随访进展至透析患者,其基线血清miR-200b与miR-200c水平较未进入透析组偏高(P＜0.05);随访尿蛋白完全缓解的患者,其基线血清miR-200a、miR-200b及miR-429水平较未完全缓解组患者偏低(P＜0.05).预后分析提示,在IgAN中,低表达水平的血清miR-200a、miR-200b水平可预测较好的尿蛋白缓解情况(P＜0.05);高表达水平的血清miR-200c可预测进展至透析的肾功能情况(P=0.042).结论:IgAN患者血清miR-200a、miR-141、miR-429表达增加.血清miR-200b、miR-141、miR-429与尿蛋白排泄密切相关,血清miR-200b、miR-200c、miR-141、miR-429水平与IgAN患者肾功能密切相关.血清miR-200a、miR-200c、miR-429水平与IgAN患者肾脏病变活动密切相关,而血清miR-200b、miR-429同时与肾小球硬化程度密切相关.IgAN患者血清miR-200家族表达的高度一致性,可能作为IgAN患者肾小管间质纤维化的生物学标记物.预后分析表明,血清miR-200c水平可预测IgAN患者肾功能进展及预后.血清miR-200a、miR-200b水平可预测IgAN患者尿蛋白缓解情况的预后.%Objective:To explore the serum miR-200 family(miR-200a、miR-200b、miR-200c、miR-141 、miR-429) in IgA nephropathy(IgAN) patients,and the relation between its expression and clinical,pathological and prognostic indicators.Further to elucidate whether serum miR-200 family could be used as a biological marker reflecting the progression and prognosis in IgAN.Methods:Studied 33 patients with biopsy-proven IgAN as IgAN group,15 healthy volunteers as healthy control group,To explore the serum expression of miR-200 family through real-time PCR,to compare miR-200 family levels and correlation between two groups.Results:As compared with control group,the serum expression of miR-200a,miR-141 and miR-429 in IgAN group were increased (P ＜0.05).Serum expression of miR-200b,miR-141 and 1niR-429 were positively correlated with proteinuria (r =0.413,P =0.021;r =0.452,P =0.014;r =0.370,P =0.040);serum expression of miR-200b,miR-200c,miR-141 and miR-429 were inversely correlated with eGFR (r =-0.403,P =0.020;r =-0.517,P =0.002;r =-0.398,P =0.024;r =-0.350,P =0.046);serum expression of miR-200a,miR-200c and miR-429 were positively correlated with degree of hematuria (r =0.361,P =0.036;r =0.367,P =0.033;r =0.397,P =0.020);serum expression of miR-200b and miR-429 were positively correlated with glomerulosclerosis (r =0.377,P =0.034;r =0.335,P =0.047) in IgAN group.Serum expression of miR-200a,miR-200b,miR-200c,miR-141 and miR-429 were positively correlated each other in IgAN group.Follow-up to the patients who developed into dialysis,base-line serum expression of miR-200b and miR-200c were higher than that did not enter dialysis.Follow-up to the patients who developed into proteinuria complete remission,base-line serum expression of miR-200a,miR-200b and miR-429 were lower than that did not enter proteinuria complete remission.Prognostic analysis showed that low expression of serum miR-200a and miR-200b could predict better urinary protein remission (P ＜ 0.05);high expression of serum miR-200c could predict renal function progressing into dialysis status (P =0.042).Conclusion:The serum expression of miR-200a,miR-141 and miR-429 were significantly increased of patients with IgAN.Serum miR-200b,miR-141 and miR-429 levels were closely related to proteinuria,and serum miR-200b,miR-200c,miR-141 and miR-429 levels were closely related to the renal function in patients with IgAN.Serum miR-200a,miR-200c and miR-4429 levels were closely related to activity of kidney disease,what is more,serum miR-200b and miR-429 levels were closely related to glomerulosclerosis.Serum expression of miR-200 family were high degree of consistency,could be considered as biological marker of tubular-interstitial fibrosis in patients with IgAN.Prognostic analysis suggest that serum miR-200c level conld predict the progression of renal function,and serum miR-200a,miR-200b could predict the remission of urinary protein in IgAN.
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