IgA肾病患者血清miR-200家族水平检测及临床意义

The Serum miR-200 Family Levels and Clinical Significance in Patients with IgA Nephropathy

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e GFR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 ex- plore 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 miR- 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 ex- pression 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 -429 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 could predict the progression of renal function, and serum miR - 200a, miR -200b could predict the remission of urinary protein in IgAN.