miR-9、miR-214在糖尿病肾病中的表达及临床意义

白小岗; 王晶; 白婷; 王延峰; 李霞

doi:10.3969/j.issn.1671-2390.2021.12.003

摘要: 目的检测微小RNA-9（microRNA-9，miR-9）、微小RNA-214（microRNA-214，miR-214）在糖尿病肾病（diabetic nephropathy，DN）患者血浆中表达水平，探讨miR-9、miR-214在DN的临床意义。方法选择2018年3月至2020年6月延安大学附属医院收治的DN患者113例为DN组，根据尿白蛋白/肌酐比值（albumin/creatinine ratio，ACR）分组分为微量白蛋白尿组（ACR 30~300 mg/g）63例，大量白蛋白尿组（ACR>300 mg/g）50例，选取同期单纯2型糖尿病患者115名作为糖尿病组，选取同期体检健康志愿者115名作为对照组，采用实时荧光定量PCR（quantitative real-time PCR，qRT-PCR）法检测各研究对象血浆miR-9、miR-214表达水平。Pearson法分析血浆miR-9、miR-214表达水平与生化指标的相关性，ROC曲线分析miR-9、miR-214表达对DN预测价值。结果与对照组比较，糖尿病组与DN组糖化血红蛋白（glycated hemoglobin，HbA1c）、总胆固醇（total cholesterol，TC）、三酰甘油（triglycerides，TG）、尿酸（uric acid，UA）、血肌酐（serum creatinine，Scr）、胱抑素C（Cystatin C，CysC）、miR-9水平显著升高，miR-214、估算肾小球滤过率（glomerular filtration rate，eGFR）水平显著降低，差异有统计学意义（P<0.05）；与糖尿病组比较，DN组HbA1c、TC、TG、UA、CysC、Scr、miR-9水平显著升高，miR-214、eGFR水平降低，差异有统计学意义（P<0.05）；与轻度DN组比较，中重度DN患者血浆miR-9水平显著升高，miR-214水平显著降低，差异有统计学意义（P<0.05）；DN患者血浆miR-9与CysC、Scr呈正相关（P<0.05），与eGFR水平呈负相关（P<0.05），miR-214表达水平与CysC、Scr呈负相关（P<0.05），与eGFR水平呈正相关（P<0.05）；血浆miR-9、miR-214联合预测DN的敏感度为88.50%，特异度为85.22%，曲线下面积为0.921。结论 DN患者血浆中miR-9明显高表达、miR-214低表达，与DN严重程度有关，可能作为诊断DN患者潜在的标志物。

Abstract: Objective To detect the plasma expression levels of microRNA-9 (miR-9) and microRNA-214 (miR-214) in patients with diabetic nephropathy (DN) and explore the clinical significance of miR-9 and miR-214 in DN.Methods From March 2018 to June 2020,113 hospitalized DN patients were divided into two groups of microalbuminuria (ACR:30~300 mg/g,n=63) and large albuminuria (ACR>300 mg/g,n=50) according to the albumin/creatinine ratio (ACR).And 115 healthy volunteers were selected as control group.Plasma levels of miR-9/miR-214 were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR).Pearson's method was utilized for examining the correlations between plasma expression levels of miR-9/miR-214 and biochemical parameters.Receiver operating characteristic (ROC) curve was plotted for analyzing the predictive value of miR-9/miR-214 expression in DN.Results Compared with those in control group,the levels of glycosylated hemoglobin (HbA1c),total cholesterol (TC),triglyceride (TG),uric acid (UA),cystatin C (CysC),serum creatinine (Scr) and miR-9 were significantly elevated while the levels of miR-214 and estimated glomerular filtration rate (eGFR) dropped markedly in diabetic and DN groups (P<0.05);compared with those in diabetic group,the levels of HbA1c,TC,TG,UA,CysC,SCr and miR-9 were significantly higher while the levels of miR-214 and eGFR lower in DN group (P<0.05);Compared with microalbuminuria group,plasma level of miR-9 spiked markedly and miR-214 level dropped significantly in macroalbuminuria group (P<0.05);plasma expression of miR-9 was correlated positively with CysC/SCr (P<0.05) and negatively with eGFR (P<0.05).And plasma expression of miR-214 was correlated negatively with CysC/SCr (P<0.05) and positively with eGFR (P<0.05);the sensitivity,specificity and area under curve (AUC) of miR-9/miR-214 were 88.50%,85.22% and 0.921 respectively.Conclusion Plasma expression of miR-9 is significantly higher and the expression of miR-214 lower in DN patients.Correlated with the severity of DN,miR-9 and miR-214 may be employed as potential diagnostic markers for DN.

miR-9、miR-214在糖尿病肾病中的表达及临床意义

Expressions and clinical significance of miR-9 and miR-214 in diabetic nephropathy