miR-34a在IgA肾病患者表达及其可能的生物标志物作用

The Expression of miR-34a and its Potential Role as Biomarkers in Patients with IgA Nephropathy

目的:探讨Ig A肾病(Ig AN)患者血清、尿液及肾组织microRNA-34a(miR-34a)表达及其与临床、病理及预后等指标的相关关系,进而探讨miR-34a作为反映Ig AN进展及预后的生物学标志物可行性。方法:收集新发33例Ig A肾病患者血清、尿液及肾组织标本(Ig AN组),来自于15例健康志愿者血清和尿液标本(健康对照组),来源于15例肾癌行肾脏切除的患者的癌旁正常肾组织(对照组),用荧光实时定量PCR行血清、尿液和肾组织miR-34a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,Ig AN组血清、尿液及肾组织miR-34a表达上调(P<0.05)。Ig AN患者血清、尿液和肾组织miR-34a表达与尿蛋白水平呈正相关关系,与e GFR负相关;血清miR-34a与肾小球硬化程度正相关;尿液miR-34a水平与新月体比例、血尿程度正相关;肾组织miR-34a水平与总胆固醇、LDL、肾小球硬化、Lee分级、肾间质纤维化及舒张压呈正相关关系,与血清白蛋白水平负相关。随访进展至透析患者,其基线尿液miR-34a水平较未进入透析组偏高(P=0.029)。预后分析提示,低表达水平的肾组织miR-34a水平可预测较好的尿蛋白缓解情况(P=0.005)。结论:Ig AN患者血清、尿液及肾组织miR-34a表达增加。血清、尿液及肾组织miR-34a水平与Ig AN患者肾功能与尿蛋白水平密切相关。尿液miR-34a水平与Ig AN患者肾脏活动病变及Ig AN肾功能进展密切相关;血清miR-34a可能作为反应肾小球硬化程度的生物学标志物。肾组织miR-34a水平与Ig AN患者肾小球硬化及肾小管间质纤维化密切相关,其过程可能与脂质代谢紊乱有关。肾组织miR-34a水平可预测Ig AN患者尿蛋白缓解情况,可作为反映Ig AN患者预后的重要生物学标志物。

Objective：To explore the urinary,serum and intra-renal expression of miR-34 a in Ig A nephropathy（ Ig AN）patients,and its correlation with clinical,pathological and prognostic indicators. Further to elucidate whether miR-34 a could be used as a biological marker reflecting the progression and prognosis in Ig AN. Methods：Studied 33 patients with biopsy-proven Ig AN as Ig AN group,serum and urine from 15 healthy volunteers as healthy control group,normal renal tissue from the nephrectomy specimen of 15 patients with renal cell carcinoma as control group. To explore the urinary,serum and intra-renal expression of miR-34 a through real-time PCR,to compare miR-34 a level and correlation between the two groups. Results：While comparing with control group,the urinary,serum and intra-renal expression of miR-34 a in Ig AN group were increased（ P 〈 0. 05）. Serum,urinary and intra-renal expression of miR-34 a were positively correlated with proteinuria,and inversely correlated with e GFR in Ig AN group.Serum expression of miR-34 a was positively correlated with glomerulosclerosis？ in Ig AN group. Urinary expression of miR-34 a was positively correlated with crescent and the degree of hematuria in Ig AN group. Intra-renal expression of miR-34 a was positively correlated with total cholesterol,LDL,glomerulosclerosis,Lee grade,renal interstitial fibrosis and diastolic blood pressure; and inversely correlated with serum albuminin in Ig AN group. Follow-up to the patients who developed into dialysis,basic urinary miR-34 a level was higher than that did not enter dialysis（ P = 0. 029）. Prognostic analysis showed that low expression of intra-renal miR-34 a could predict better urinary protein remission（ P = 0. 005）. Conclusion：The serum,urinary and intra-renal expression of miR-34 a were significantly increased of patients with Ig AN. Serum,urinary and intra-renal miR-34 a levels were closely related to the renal function and proteinuria in patients with Ig AN. Urinary expression of miR-34 a was closely related to activity of kidney injury and progression of renal function,and serum level of miR-34 a could be used as an biological indicators to reflect the degree of glomerulosclerosis in patients with Ig AN. Intra-renal expression of miR-34 a was closely related to tubular-interstitial fibrosis and the degree of glomerulosclerosis,the process might be related to lipid metabolism disorders. Intra-renal expression of miR-34 a could predict the remission of urinary protein,could be considered as biological marker,reflecting the prognosis of Ig AN.