IgA肾病患者尿液外泌体中微小RNA-146a、微小RNA-210表达及与病理分级的相关性研究

Expressions of miR-146a and miR-210 in urinary exosomes of patients with IgA nephropathy and its correlation with histological grade

目的探索IgA肾病(IgA nephropathy,IgAN)患者尿液外泌体中微小RNA(miRNA,miR)-146a、miR-210表达及其与IgAN病理分级的相关性。方法选取2018年1月至2022年1月在雅安市人民医院经肾穿刺后病理组织学活检确诊的IgAN患者113例作为研究对象,并选取同期健康体检人群100人作为健康对照组。将研究对象的肾脏病理标本按照Lee氏分级分为轻(Ⅰ-Ⅱ级)、中(Ⅲ级)、重(Ⅳ-Ⅴ)3组,实时荧光定量PCR比较实验组及健康对照组两组间尿液外泌体中miR-146a、miR-210表达水平;比较不同病理分级IgAN患者尿液外泌体中miR-146a、miR-210表达水平;Spearman秩相关系数分析IgAN患者24 h尿蛋白、血肌酐、尿液外泌体miR-146a及miR-210表达水平之间的相关性;采用受试者工作特征曲线评估尿液外泌体中miR-146a、miR-210表达对IgAN的诊断价值。结果IgAN患者尿液外泌体中miR-146a[(3.27±1.59)比(5.13±0.34)]、miR-210[(1.25±0.71)比(2.33±0.45)]表达较健康对照组明显降低(P<0.01);IgAN患者尿液外泌体中miR-146a、miR-210表达水平与Lee氏分级、24 h尿蛋白及血肌酐呈负相关,即Lee氏分级越高,其表达水平越低。miR-146a用于诊断IgAN的敏感度及特异度分别为88.89%、77.52%,曲线下面积为0.835;miR-210用于诊断IgAN的敏感度及特异度分别为79.71%、85.92%,曲线下面积为0.842。结论IgAN患者尿液外泌体中miR-146a、miR-210表达水平明显降低,对尿液外泌体中miR-146a、miR-210表达水平进行检测有助于对IgAN病理分级进行判断,尿液外泌体中miR-146a、miR-210有望作为IgAN辅助诊断和治疗效果监测的潜在分子标志物。

Objective To explore the expressions of miR-146a and miR-210 in urinary exosomes of patients with IgAN(IgA nephropathy)and examine their correlation with histological grade of IgAN.Methods From January 2018 to January 2022,113 patients were confirmed as IgAN by histopathology after renal biopsy and selected as research group.Another 100 healthy subjects undergoing physical examination during the same period were selected as healthy control group.According to Lee's classification,they were divided into three groups of mild(gradeⅠ-Ⅱ),moderate(gradeⅢ)and severe(gradeⅣ-Ⅴ).The expression levels of miR-146a and miR-210 in urinary exosomes of IgAN patients with different histological grades were compared;Spearman’s rank correlation coefficient was utilized for examining the correlation among 24 h urinary protein,serum creatinine,miR-146a and miR-210 expression levels;receiver operating characteristic curve was plotted for evaluating the diagnos-tic values of miR-146a and miR-210 in urinary exosomes for IgAN.Results The expressions of miR-146a in urinary exosomes of IgAN patients were significantly lower than those of healthy control group[(3.27±1.59)vs(5.13±0.34)]and miR-210[(1.25±0.71)vs(2.33±0.45)](P<0.01).Histological grade,24 h urinary protein and serum creatinine were correlated negatively with the expressions of miR-146a and miR-210.That is,the higher the Lee's grade,the lower the expression levels of miR-146a and miR-210.The sensitivity and specificity of miR-146a for diagnosing IgAN were 88.89%and 77.52%and the area under the curve was 0.835;the sensitivity and specificity of miR-210 for diagnosing IgAN were 79.71%and 85.92%,and the area under the curve was 0.842.Conclusion The expression levels of miR-146a and miR-210 decline markedly in urinary exosomes of IgAN patients.Detecting the expression levels of miR-146a and miR-210 in urinary exosomes helps to assess the histological grades of IgAN.miR-146a and miR-210 in urinary exosomes are expected to be potential molecular biomarkers for auxiliary diagno-sis and monitoring of therapeutic efficacy for IgAN.