血清miR-29联合LncRNA TUG1与ADMA对缺血性脑卒中的鉴别诊断价值

The differential diagnosis value of serum miR-29 combined with lncRNA TUG1 and ADMA in ischemic stroke

目的探讨血清微小RNA-29(miR-29)联合长链非编码RNA(lncRNA)TUG1及非对称二甲基精氨酸(ADMA)对缺血性脑卒中的鉴别诊断价值。方法收集2017年6月-2018年7月本院确诊的缺血性脑卒中患者110例,选取出血性脑卒中患者80例,同期纳入本院的体检健康者100例;采用实时荧光定量PCR(RT-PCR)法检测血清miR-29和LncRNA TUG1表达水平;采用酶联免疫吸附法(ELISA)检测血清ADMA水平。结果与出血性脑卒中组miR-29(60.7±4.3)-log,LncRNA TUG1(16.4±1.4)-log,ADMA(6.3±0.7) mIU/mL和健康对照组miR-29(62.3±4.8)-log;LncRNA TUG1(15.9±1.3)-log;ADMA(6.4±0.6) mIU/mL比较,缺血性脑卒中组血清LncRNA TUG1(43.5±3.5)-log和ADMA(11.4±1.4) mIU/mL水平显著升高,而血清miR-29(31.4±2.1)-log水平显著降低(P<0.05),而出血性脑卒中组和健康对照组血清miR-29、LncRNA TUG1及ADMA水平无明显差异(P>0.05)。Spearman相关性分析显示,血清LncRNA TUG1及ADMA水平与NIHSS评分(LncRNA TUG1:r=0.538,P=0.002;ADMA:r=0.566,P=0.001)呈正相关,而血清miR-29水平与NIHSS评分(miR-29:r=-0.545,P=0.001)呈负相关。血清miR-29、LncRNA TUG1及ADMA区分缺血性脑卒中与非缺血性脑卒中(出血性脑卒中和健康对照者)的AUC分别为0.863(95%CI=0.800~0.944,P<0.001)、0.912(95%CI=0.833~0.977,P<0.001)和0.764(95%CI=0.688~0.887,P<0.001);敏感度及特异度分别为85.3%/82.1%、94.2%/73.5%和76.8%/81.2%;对应的临界值分别为48.6-log、33.2-log和9.5 mIU/mL。当联合血清miR-29、LncRNA TUG1及ADMA时区分缺血性脑卒中与非缺血性脑卒中的AUC为0.945(95%CI=0.932~0.998,P<0.001),敏感度为83.8%,特异度为97.3%。结论联合血清miR-29、LncRNA TUG1及ADMA对缺血性脑卒中具有潜在的鉴别诊断价值。

Objective To explore the differential diagnosis value of serum microRNA-29(miR-29) combined with long non-coding RNA(lncRNA) TUG1 and asymmetric dimethylarginine(ADMA) in ischemic stroke.Methods 110 patients with ischemic stroke diagnosed in our hospital from June 2017 to July 2018 were collected. 80 patients with hemorrhagic stroke were selected, and 100 healthy people were included in our hospital during the same period. Real-time PCR(RT-PCR) was used to detect the expression levels of serum miR-29 and LncRNA TUG1, and enzyme-linked immunosorbent assay(ELISA) was used to detect the level of serum ADMA.Results Compared with hemorrhagic stroke[miR-29:(60.7±4.3)-log, LncRNA TUG1:(16.4±1.4)-log, ADMA:(6.3±0.7) mIU/mL]and healthy controls(miR-29:(62.3±4.8)-log, LncRNA TUG1:(15.9±1.3)-log, ADMA:(6.4±0.6) mIU/mL], serum LncRNA TUG1(43.5±3.5)-log and ADMA(11.4±1.4) mIU/mL levels in patients with ischemic stroke were significantly increased(P<0.05), and the level of serum miR-29(31.4±2.1(-log))was significantly decreased(P<0.05). The levels of serum miR-29, LncRNA TUG1 and ADMA were not significantly different between hemorrhagic stroke and healthy controls(P>0.05). Spearman correlation analysis showed that serum levels of LncRNA TUG1 and ADMA were positively correlated with NIHSS score(LncRNA TUG1:r=0.538, P=0.002;ADMA:r=0.566, P=0.001), while serum level of miR-29 was negatively correlated with NIHSS score(mir-29:r=-0.545,P=0.001). The AUC of serum miR-29, LncRNA TUG1 and ADMA for ischemic stroke and non-ischemic stroke(hemorrhagic stroke and healthy controls) were 0.863(95% CI=0.800~0.944, P<0.001), 0.912(95% CI=0.833~0.977, P<0.001) and 0.764(95% CI=0.688~0.887, P<0.001);sensitivity and specificity were 85.3%/82.1%, 94.2%/73.5% and 76.8%/81.2%. The corresponding critical values were 48.6(-log), 33.2(-log) and 9.5 mIU/mL. When combined with serum miR-29, LncRNA TUG1 and ADMA, the AUC of ischemic stroke and non-ischemic stroke was 0.945(95%CI=0.932~0.998, P<0.001), and the sensitivity was 83.8%, the specificity was 97.3%.Conclusion Combined serum miR-29, LncRNA TUG1 and ADMA had potential diagnostic value in ischemic stroke.