miR-145、miR-146a在慢性阻塞性肺疾病合并冠心病患者血清中的表达及临床意义

Expressions and clinical significance of serum miR-145 and miR-146a in the patients with chronic obstructive pulmonary disease and coronary heart disease

目的探究慢性阻塞性肺疾病(COPD)合并冠心病(CHD)患者血清miR-145、miR-146a的表达水平及临床意义。方法收集2014年至2019年本院就诊的COPD稳定期患者96例,以COPD稳定期合并CHD患者38例作为COPD+CHD组,COPD稳定期未合并CHD患者58例作为COPD组,另选取同期在本院体检健康者45例作为健康人对照组。采用实时荧光定量PCR(qRT-PCR)检测各组血清miR-145、miR-146a的表达水平,并分析其与C反应蛋白(CRP)、纤维蛋白水平、肺功能、血气指标及Gensini评分关系。结果健康人对照组、COPD组、COPD+CHD组血清miR-145(1.01±0.32 vs 0.73±0.25 vs 0.47±0.14)、miR-146a(0.99±0.28 vs 0.81±0.21 vs 0.45±0.13)的表达水平依次降低,差异有统计学意义(F分别为47.429、64.532,P均<0.05)。COPD+CHD组患者血清miR-145、miR-146a水平分别与CRP、纤维蛋白原水平及Gensini评分呈负相关(r分别为-0.398/-0.384、-0.403/-0.395、-0.407/-0.413,P均<0.05),而与肺功能指标FEV1/FVC、血气指标PaO2水平呈正相关(r分别为0.421/0.405、0.357/0.362,P均<0.05)。此外,高CRP水平、低PaO2水平、低FEV1/FVC水平、高Gensini评分、低miR-145水平、低miR-146a水平是影响COPD并发CHD的独立危险因素(P均<0.05)。血清miR-145、miR-146a联合诊断COPD合并CHD的曲线下面积(AUCROC)为0.887(95%CI:0.821~9.520),明显高于miR-145、miR-146a单独诊断。结论血清miR-145及miR-146a表达下调与COPD患者肺功能降低、病情加重有关,是患者并发CHD的独立危险因素。

Objective To investigate the expression and significance of serum miR-145 and miR-146a in the patients with chronic obstructive pulmonary disease(COPD)and coronary heart disease(CHD).Methods A total of 96 patients with stable COPD admitted in our hospital during 2014 and 2019,including 38 stable COPD patients with CHD(COPD+CHD group)and 58 stable COPD patients without CHD(COPD group),were enrolled.In addition,45 healthy persons who were examined in our hospital during the same period were selected as the control group.The expression levels of serum miR-145 and miR-146a in these patients and healthy controls were detected by the real-time fluorescence quantitative PCR(qRT-PCR),and their relationships with CRP,fibrinogen levels,lung function,blood gas indexes and Gensini score were analyzed.Results The levels of serum miR-145(1.01±0.32 vs 0.73±0.25 vs 0.47±0.14)and miR-146a(0.99±0.28 vs 0.81±0.21 vs 0.45±0.13)in the control,COPD and COPD+CHD groups were decreased in turn,and there was statistical significance in the difference among them(F=47.429 and 64.532,P<0.05).The levels of serum miR-145 and miR-146a in the COPD+CHD group were negatively correlated with CRP levels(r=-0.398 and-0.384,P<0.05),fibrinogen levels(r=-0.403 and-0.395,P<0.05)and Gensini scores(r=-0.407 and-0.413,P<0.05),and positively correlated with lung function index FEV1/FVC(r=0.421 and 0.405,P<0.05)and blood gas index PaO2(r=0.357 and 0.362,P<0.05),respectively.In addition,the high CRP level,low PaO2 level,low FEV1/FVC level,high Gensini score,low miR-145 level and low miR-146a level were the independent risk factors of COPD complicated with CHD(P<0.05).The area under the curve(AUCROC)of serum miR-145 and miR-146 in the combination diagnosis of COPD complicated with CHD was 0.887(95%CI:0.821-9.520),which was significantly higher than that of miR-145 and miR-146a alone.Conclusion The down-regulation of serum miR-145 and miR-146a is associated with decreased lung function and exacerbation of COPD,which are independent risk factors of COPD patients complicated with CHD.