血清miR-486-5p和miR-195-5p在慢性阻塞性肺疾病患者中的表达水平及临床意义

Expression levels and clinical significance of serum miR-486-5p and miR-195-5p in patients with chronic obstructive pulmonary disease

目的探讨慢性阻塞性肺疾病(COPD)患者血清微小RNA(miR)-486-5p和miR-195-5p水平与病情严重程度的关系。方法选取2022年5月至2023年4月于该院就诊的102例COPD患者纳入COPD组,根据COPD全球倡议(GOLD)评分,将COPD患者分为急性加重COPD组(AECOPD组)54例和稳定COPD组(SCOPD组)48例,根据病情严重程度分为Ⅰ级17例、Ⅱ级27例、Ⅲ级33例、Ⅳ级25例。并招募同期于该院进行体检的100例健康志愿者作为对照组。收集所有研究对象基线资料及肺功能指标,采用实时荧光定量聚合酶链反应检测COPD患者血清miR-486-5p、miR-195-5p水平。采用Spearman或Pearson相关分析血清miR-486-5p、miR-195-5p水平与临床指标的相关性。采用受试者工作特征(ROC)曲线分析血清miR-486-5p、miR-195-5p对AECOPD的诊断价值。结果AECOPD组、SCOPD组第1秒用力呼气容积(FEV1)占预计值百分比(FEV1%pred)、FEV1与用力肺活量(FVC)比值(FEV1/FVC)及血清miR-486-5p、miR-195-5p水平低于对照组,白细胞计数高于对照组,差异均有统计学意义(P<0.05);AECOPD组动脉血二氧化碳分压(PaCO 2)、白细胞计数、mMRC明显高于SCOPD组,FEV1%pred、FEV1/FVC、氧合指数(PaO 2/FiO 2)及血清miR-486-5p、miR-195-5p低于SCOPD组,差异均有统计学意义(P<0.05)。血清miR-486-5p、miR-195-5p及二者联合检测诊断AECOPD的曲线下面积(AUC)分别为0.865、0.843、0.912,其中二者联合检测诊断AECOPD的AUC明显高于2项指标单独检测的AUC(Z=1.963、2.211,P<0.05)。COPD患者血清miR-486-5p、miR-195-5p水平与FEV1%pred、FEV1/FVC、PaO 2/FiO 2呈正相关(r=0.497、0.614、0.332,0.512、0.572、0.353,P<0.05),血清miR-486-5p、miR-195-5p水平与PaCO 2、mMRC呈负相关(r=-0.327、-0.553,-0.341、-0.518,P<0.05)。血清miR-486-5p、miR-195-5p水平在Ⅰ、Ⅱ、Ⅲ、Ⅳ级COPD患者中依次降低,两级间比较,差异均有统计学意义(P<0.05)。结论COPD患者血清miR-486-5p、miR-195-5p水平下降,且与病情严重程度及肺功能指标存在相关性,可作为临床评估COPD患者病情的新指标。

Objective To investigate the correlation between serum levels of microRNA(miR)-486-5p and miR-195-5p in patients with chronic obstructive pulmonary disease(COPD)and the severity of the condition.Methods A total of 102 cases COPD patients in the Second People's Hospital of Jiulongpo District from May 2022 to April 2023 were collected as the study subjects(COPD group),according to the COPD Global Initiative(GOLD)score,COPD patients were separated into acute exacerbation COPD group(AECOPD group)of 54 cases and stable COPD group(SCOPD group)of 48 cases,according to the severity of the condition,there were 17 cases of grade Ⅰ,27 cases of grade Ⅱ,33 cases of grade Ⅲ,and 25 cases of grade Ⅳ.A total of 100 individuals who went to this hospital for physical examination were recruited as the control group.Baseline data and lung function indicators of enrolled individuals were collected,real-time fluorescence quantitative polymerase chain reaction was applied to detect the expression levels of miR-486-5p and miR-195-5p in serum of COPD patients.Spearman or Pearson correlation was applied to analyze the correlation between serum miR-486-5p,miR-195-5p levels and clinical indicators.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum miR-486-5p and miR-195-5p for the occurrence of AECOPD.Results The levels of first second forced expiratory volume(FEV1)as a percentage of expected value(FEV1%pred),the ratio of FEV1 and forced vital capacity(FEV1/FVC),serum miR-486-5p and miR-195-5p in the AECOPD group and SCOPD group were lower than those in the control group,and the white blood cell count was higher than that in the control group,with statistical significance(P<0.05).The arterial carbon dioxide partial pressure(PaCO 2),white blood cell count and mMRC in the AECOPD group were significantly higher than those in the SCOPD group,FEV1%pred,FEV1/FVC,oxygenation index(PaO 2/FiO 2),the serum miR-486-5p and miR-195-5p were lower than those in the SCOPD group,the differences were statistically significant(P<0.05).The area under the curve(AUC)of serum miR-486-5p,miR-195-5p,and combined detection for diagnosing AECOPD were 0.865,0.843 and 0.912 respectively.Among them,the AUC of combined detection for diagnosing AECOPD was significantly higher than that of the two indicators tested separately(Z=1.963,2.211,P<0.05).The serum levels of miR-486-5p and miR-195-5p in COPD patients correlated positively with FEV1%pred,FEV1/FVC,PaO 2/FiO 2(r=0.497,0.614,0.332;0.512,0.572,0.353,P<0.05).The levels of serum miR-486-5p and miR-195-5p correlated negatively with PaCO 2 and mMRC(r=-0.327,-0.553;-0.341,-0.518,P<0.05).Serum levels of miR-486-5p and miR-195-5p decreased sequentially in COPD patients of grades Ⅰ,Ⅱ,Ⅲ and Ⅳ,the differences between the two grades were statistically significant(P<0.05).Conclusion The serum levels of miR-486-5p and miR-195-5p in COPD patients decrease,and there is a correlation with the severity of the condition and lung function indicators,which can be used as a new clinical indicator for evaluating the condition of COPD patients.