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微小RNA-21和程序性细胞死亡因子4在慢性阻塞性肺疾病患者支气管肺泡灌洗液肺泡巨噬细胞中的表达研究

Expressions of miR-21 and programmed cell death factor 4 in alveolar macrophages of bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease

    摘要
  • 摘要:
      目的  探讨微小RNA-21（miR-21）、程序性细胞死亡因子4（PDCD4）在慢性阻塞性肺疾病（COPD）患者支气管肺泡灌洗液（BALF）肺泡巨噬细胞（AM）中的表达水平及意义。
      方法  选取135例COPD患者进行研究（COPD组），依据患者病情分为COPD稳定组62例、COPD急性加重期（AECOPD）组73例；并选取同期因喉部异物感等原因做纤支镜检查的健康者73例进行对照研究（正常组）。比较COPD组与正常组一般资料；采用实时荧光定量聚合酶链反应（qRT-PCR）检测BALF AM中miR-21、PDCD4 mRNA相对表达量；Pearson法分析COPD患者BALF AM中miR-21、PDCD4 mRNA表达水平与肺功能指标，miR-21表达水平与PDCD4 mRNA的相关性；采用受试者工作特征曲线（ROC）评估BALF AM中miR-21、PDCD4 mRNA表达水平对COPD的诊断价值。
      结果  与正常组相比，COPD组患者第1秒用力呼气容积（FEV1）占预计值百分比（FEV1%）及FEV1/用力肺活量（FVC）水平均降低，差异有统计学意义（P < 0.05）；与正常组相比，COPD稳定组、AECOPD组患者BALF AM中miR-21表达水平均升高，PDCD4 mRNA表达水平均降低，差异有统计学意义（P < 0.05）；与COPD稳定组相比，AECOPD组患者BALF AM中miR-21表达水平升高，PDCD4 mRNA表达水平降低，差异有统计学意义（P < 0.05）；COPD患者BALF AM中miR-21表达水平与PDCD4 mRNA水平、FEV1%、FEV1/FVC均呈负相关（P < 0.05），PDCD4 mRNA表达水平与FEV1%、FEV1/FVC均呈正相关（P < 0.05）；BALF AM中miR-21、PDCD4 mRNA对COPD诊断的曲线下面积（AUC）为0.844、0.849，相应截断值分别为1.54、0.70，灵敏度分别为70.4%、77.8%，特异度分别为86.3%、80.8%；两者联合诊断COPD的AUC为0.903，其灵敏度、特异度分别为90.4%、84.9%。
      结论  COPD患者BALF AM中miR-21表达升高，PDCD4表达降低，miR-21可能与PDCD4相互影响，进而协同影响COPD病变过程，两者水平有助于临床筛查COPD患者及评估患者病情。

     

    Abstract:
      Objective  To investigate the expression levels of miR-21 and programmed cell death factor 4 (PDCD4) in alveolar macrophages (AM) of bronchoalveolar lavage fluid (BALF) in patients with chronic obstructive pulmonary disease (COPD).
      Methods  A total of 135 COPD patients were selected as study objects (COPD group). According to the patients' conditions, they were divided into stable COPD group (62 cases) and acute exacerbation stage of COPD (AECOPD) group (73 cases); a total of 73 healthy people who underwent bronchoscopy due to laryngeal foreign body sensation were selected for control study (normal group). The general data of COPD group and normal group were compared; real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-21 and PDCD4 mRNA in BALF AM; Pearson method was used to analyze the correlations between the expression of miR-21 and PDCD4 mRNA in BALF AM and lung function indexes, and the correlation between miR-21 expression level and PDCD4 mRNA expression level; receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-21 and PDCD4 mRNA in BALF AM for COPD.
      Results  Compared with the normal group, the percentage of forced expiratory volume in the first second (FEV1) in expected value (FEV1%) and FEV1/forced vital capacity (FVC) level in the COPD group were significantly decreased (P < 0.05); compared with the normal group, the expression levels of miR-21 in BALF AM were significantly higher, and the expression levels of PDCD4 mRNA were significantly lower of patients in the stable COPD group and AECOPD group (P < 0.05); compared with the stable COPD group, the expression level of miR-21 in BALF AM of the AECOPD group was significantly higher, and the expression level of PDCD4 mRNA was significantly lower (P < 0.05); the expression levels of miR-211 in BALF AM of COPD patients were negatively correlated with PDCD4 mRNA level, FEV1% and FEV1/FVC (P < 0.05), while PDCD4 mRNA expression was positively correlated with FEV1% and FEV1/FVC (P < 0.05); the area under the curve (AUC) of miR-21 and PDCD4 mRNA in BALF AM were 0.844 and 0.849, corresponding cut-off value were 1.54 and 0.70, sensitivity were 70.4% and 77.8%, specificity were 86.3% and 80.8%, respectively; the AUC of the combined diagnosis of COPD was 0.903, and its sensitivity and specificity were 90.4% and 84.9%, respectively.
      Conclusion  The expression of miR-21 in BALF AM of COPD patients is increased, and the expression of PDCD4 is decreased. MiR-21 may interact with PDCD4, and then synergistically affect the pathological process of COPD. Both levels are helpful for clinical screening of COPD patients and evaluation of patients' condition.

     

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