血清miR-92a和miR-146a表达水平联合肺部超声评分预测ARDS严重程度及预后的价值

The value of serum microRNA-92a and microRNA-146a levels combined with pulmonary ultrasound score in predicting the severity and prognosis of acute respiratory distress syndrome

目的探讨血清微小RNA-92a(miR-92a)和微小RNA-146a(miR-146a)表达水平联合肺部超声评分(LUS)预测急性呼吸窘迫综合征(ARDS)严重程度及预后的价值。方法选择2017年1月至2020年3月儋州市人民医院收治的116例ARDS患者。于患者入院当日,采用实时荧光定量反转录-聚合酶链反应(RT-PCR)检测血清miR-92a及miR-146a表达水平,并对12个肺区进行肺部超声检查,总分即为LUS评分。分析28 d不同预后(存活组与死亡组)以及不同程度ARDS患者〔轻度组:200 mmHg<氧合指数(OI)≤300 mmHg(1 mmHg=0.133 kPa),中度组:10 mmHg<OI≤200 mmHg,重度组:OI≤100 mmHg〕各指标的差异,应用多因素Logistic回归分析ARDS患者死亡危险因素;绘制受试者工作特征曲线(ROC),分析miR-92a及miR-146a联合LUS评分预测ARDS患者死亡的价值。结果116例ARDS患者均纳入分析,死亡组39例,存活组77例;轻度组20例,中度组38例,重度组58例。死亡组血清miR-92a及miR-146a表达水平和LUS评分均明显高于存活组〔miR-92a(2^-ΔΔCt):3.75±1.64比2.10±0.78,miR-146a(2^-ΔΔCt):1.93±0.72比0.76±0.20,LUS评分(分):25.80±4.75比13.40±3.60,均P<0.01〕。随ARDS患者病情程度加重,血清miR-92a及miR-146a表达水平和LUS评分逐渐升高(F值分别为8.115、6.740、6.216,均P<0.01)。重度组血清miR-92a及miR-146a表达水平和LUS评分均明显高于中度组和轻度组〔miR-92a(2^-ΔΔCt):3.65±1.62比2.87±1.16、1.94±0.68,miR-146a(2^-ΔΔCt):1.85±0.58比1.30±0.51、0.68±0.17,LUS评分(分):24.15±4.65比18.60±4.20、12.20±3.15,均P<0.01〕。多因素Logistic回归分析显示,OI低〔优势比(OR)=2.748,95%可信区间(95%CI)为1.913~6.225,P=0.024〕、LUS评分高(OR=1.685,95%CI为1.183~2.758,P=0.016)、血清miR-92a(OR=2.560,95%CI为1.806~5.627,P<0.001)及miR-146a(OR=1.984,95%CI为1.375~3.816,P=0.008)表达水平高是ARDS患者死亡的独立危险因素。ROC曲线分析显示,miR-92a及miR-146a联合LUS评分预测ARDS患者死亡的ROC曲线下面积(AUC)明显高于三者单独预测(0.918比0.842、0.825、0.807,均P<0.01),其敏感度和特异度均较高,分别为94.0%、85.2%。结论血清miR-92a、miR-146a表达水平和LUS评分与ARDS患者病情严重程度及预后有关,三者联合预测ARDS患者预后具有较好的价值。

Objective To investigate the value of serum microRNA-92a(miR-92a)and microRNA-146a(miR-146a)expression levels combined with lung ultrasound score(LUS)in predicting the severity and prognosis of acute respiratory distress syndrome(ARDS).Methods 116 patients with ARDS admitted to Danzhou People's Hospital from January 2017 to March 2020 were enrolled.On the day of admission,the expression levels of serum miR-92a and miR-146a were detected by real-time fluorescent quantitative reverse transcript-polymerase chain reaction(RT-PCR),and pulmonary ultrasound examination was performed in 12 lung regions,with the total score as LUS score.The difference of each index was analyzed among the ARDS patients with different 28-day prognosis(survival group and death group)and different severity[mild group:200 mmHg<oxygenation index(OI)≤300 mmHg(1 mmHg=0.133 kPa),moderate group:100 mmHg<OI≤200 mmHg,severe group:OI≤100 mmHg].Multivariate Logistic regression was used to analyze the risk factors of death in patients with ARDS.Receiver operating characteristic(ROC)curve was drawn to analyze the value of miR-92a and miR-146a combined with LUS score in predicting the death of patients with ARDS.Results 116 ARDS patients were included,39 cases in the death group,77 cases in the survival group;20 cases in the mild group,38 cases in the moderate group and 58 cases in the severe group.The expression levels of serum miR-92a,miR-146a and LUS score in the death group were significantly higher than those in the survival group[miR-92a(2^-ΔΔCt):3.75±1.64 vs.2.10±0.78,miR-146a(2^-ΔΔCt):1.93±0.72 vs.0.76±0.20,LUS score:25.80±4.75 vs.13.40±3.60,all P<0.01].With the aggravation of ARDS patients,the expression levels of serum miR-92a and miR-146a and LUS score gradually increased(F values were 8.115,6.740 and 6.216 respectively,all P<0.01).The expression levels of serum miR-92a,miR-146a and LUS score in severe group were significantly higher than those in the moderate group and mild group[miR-92a(2^-ΔΔCt):3.65±1.62 vs.2.87±1.16,1.94±0.68;miR-146a(2^-ΔΔCt):1.85±0.58 vs.1.30±0.51,0.68±0.17;LUS score:24.15±4.65 vs.18.60±4.20,12.20±3.15,all P<0.01].Multivariate Logistic regression analysis showed that low OI[odds ratio(OR)=2.748,95%confidence interval(95%CI)was 1.913-6.225,P=0.024],high LUS score(OR=1.685,95%CI was 1.183-2.758,P=0.016),high expression levels of serum miR-92a(OR=2.560,95%CI was 1.806-5.627,P<0.001)and miR-146a(OR=1.984,95%CI was 1.375-3.816,P=0.008)were independent risk factors for the death of ARDS patients.ROC curve analysis showed that the area under ROC curve(AUC)of patients with ARDS predicted by miR-92a and miR-146a combined with LUS score was significantly higher than that predicted by the three alone(0.918 vs.0.842,0.825,0.807,all P<0.01),and the sensitivity(94.0%)and specificity(85.2%)were higher.Conclusion The expression levels of serum miR-92a,miR-146a and LUS score are related to the severity and prognosis of the patients with ARDS,and the combination of the three indicators has better value in predicting the prognosis of the patients with ARDS.