糖尿病和糖尿病肾病患者血清lncRNA GAS5／miR-21的诊断效能  

The efficiency of serum IncRNA GAS5/miR- 21 as biomarkers in patients with diabetes and diabetic nephropathy

作　　者：陈桐[1] 范秋灵[1] 崔靖彬 徐莉[1] 汪旭[1] 林冬芳 王力宁[1] 

机构地区：[1]中国医科大学附属第一医院肾内科,沈阳110001

出　　处：《中华肾脏病杂志》2017年第12期906-913,共8页Chinese Journal of Nephrology

基　　金：国家自然科学基金（81270808）;辽宁省自然科学基金（201602821）;辽宁省高等学校重大科技平台免疫皮肤病重点实验室自主创新课题基金（201303）;沈阳市科技计划项目（F16-205-1-40）

摘　　要：目的检测糖尿病（DM）和糖尿病肾病（DN）患者血清lncRNA-生长停滞特异基因5（1ncRNAGAS5）和微小RNA-21（miR-21）的表达变化，分析其与临床和病理指标的相关性，明确lncRNAGAS5和miR-21对DM和DN的诊断效能。方法入组人群分为3组：DN组（肾活检病理诊断明确，n=25，男14例，女11例）、DM组（尿微量白蛋白／尿肌酐正常，n=10，男4例，女6例）和正常对照组（NC组，n=9，男4例，女5例）。空腹采血，分离血清，实时荧光定量PCR法检测基因表达。应用t检验、Pearson、Spearman检验及多元线性回归分析lncRNAGAS5及miR-21表达水平和各临床指标的相关性，单因素方差分析检验lncRNAGAS5及miR-21在不同分组中的差异性，用受试者工作特征（ROC）曲线下面积（AUC）评价lncRNAGAS5及miR-21在疾病中的诊断效能。所有数据采用SPSS20．0统计，GraphPad软件处理，P〈0．05视为差异有统计学意义。结果（1）DM和DN患者血清lncRNA GAS5的表达水平均低于正常对照组，血清miR-21的表达水平均高于正常对照组，差异有统计学意义（均P〈0．05）。（2）DN患者中，随着24h尿蛋白量的逐渐增多，血清lncRNAGAS5的表达逐渐上调。随着肾活检病理分级的进展（llb-Ⅲ期），血清miR-21的表达也上调（P〈0．05）。（3）空腹血糖（FBG）和糖化血红白蛋白（HbA1c）与血清lncRNAGAS5呈负相关（P〈0．05），并且FBG与血清lncRNAGAS5独立相关（P〈0．05）；尿微量白蛋白（MA）、总胆固醇（TC）、Scr、BUN和SBP与血清miR-21水平呈正相关（P〈0．05）；血清白蛋白（ALB）和肾小球滤过率（eGFR）与血清miR-21水平呈负相关（P〈0．05），并且ALB与血清miR-21独立相关（P〈0．05）。（4）血清lncRNAGAS5、miR-21及lncRNAGAS5／miR．21“诊断标签”诊断DM的价值较好（P〈0．05）。（5）血清miR-21及lncRNAGAS5／miR-21“诊断标签”诊断DN的价值较好（P〈0．05�Objective To elucidate the efficiency lncRNA GAS5 and miR-21 as biomarkers in diabetes mellitus and diabetic nephropathy. Methods The patients were divided into three groups, diabetic nephropathy group （DN group proven by renal biopsy, n=25, 14 males and 11 females）, diabetes group （DM group, with normal urine albumin creatinine ratio, n=10, 4 males and 6 females）, and normal control group （NC group, n=9, 4 males and 5 females）. The expressions of lncRNA GAS5 and miR-21 in serum samples were detected by real-time quantitative PCR. The correlation between serum lncRNA GAS5 and miR-21 expressions and the clinical parameters was analyzed by T-test, Pearson, Spearman test and multivariate linear regression analysis. Differences of lncRNA GAS5 and miR-21 in different groups were analyzed by one-way analysis of variance. The ROC curve was used to analyze the diagnostic efficacy of lncRNA GAS5 and miR-21 in diabetes and diabetic nephropathy. All data were analyzed by SPSS 20.0 and GraphPad software, with P 〈 0.05 as considered statistically significant. Results （1） The expression of serum lncRNA GAS5 was significantly down-regulated and serum miR-21 was significantly up-regulated in both diabetes mellitus and diabetic nephropathy patients compared to the NC group all （P 〈 0.05）. （2） In DN patients, the expression of serum lncRNA GAS5 was gradually up-regulated along with the increment of 24 h urinary protein. The expression of serum miR-21 was gradually up-regulated along with renal biopsy stage IIb-m of DN （P 〈 0.05）. （3） FBG and HbAlc were all negatively correlated with serum lncRNA GAS5 （P 〈 0.05）, and FBG was independently correlated with serum lncRNA GAS5 （P 〈 0.05）. Urine microalbumin, Total cholesterol （TC）, Scr, Urea and SBP were all positively correlated with serum miR-21（P 〈 0.05）. Albumin （ALB） and estimated GFR （eGFR） were negatively correlated with serum miR- 21（P 〈 0.05）, and ALB was independently correlated with serum miR-21 （P �

关 键 词：糖尿病肾病 糖尿病 微小RNA lncRNA生长停滞特异基因5 MIR-21 诊断标签 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]