血清窖蛋白-1在慢性阻塞性肺疾病相关肺动脉高压患者中的表达及意义

The expression and significance of serum caveolin-1 in patients with pulmonary hypertension associated with chronic obstructive pulmonary diseases

目的研究血清窖蛋白-1(Cav-1)在慢性阻塞性肺疾病(COPD)相关肺动脉高压(PAH)患者中的表达及其意义。方法选取稳定期COPD患者65例,根据是否合并PAH分成COPD组[肺动脉收缩压(PASP)<40 mmHg,35例]及COPD-PAH组(PASP≥40 mmHg,30例)。另选取在本院健康体检的志愿者30例作为对照组。对比各组基线资料、动脉血气分析、肺功能指标,以及血清Cav-1、白细胞介素(IL)-6和肿瘤坏死因子-α(TNF-α)的表达水平。绘制受试者工作特征(ROC)曲线,评价Cav-1对COPD合并PAH的诊断价值。结果 COPD-PAH组与COPD组第一秒用力呼吸容积(FEV1)/用力肺活量(FVC)、FEV1占预计值百分比(FEV1%)及氧分压[p(O_2)]低于对照组,而二氧化碳分压[p(CO_2)]、PASP均高于对照组(P<0.01)。COPD-PAH组p(O_2)低于COPD组,p(CO_2)、PASP均高于COPD组(P<0.01)。对照组、COPD组及COPD-PAH组Cav-1表达水平呈逐渐降低趋势,而IL-6、TNF-α表达水平呈逐渐升高趋势(P<0.01)。血清Cav-1诊断COPD合并PAH的ROC曲线下面积为0.902(0.821～0.955),最佳截断值为6.66μg/L,此时诊断敏感度为76.7%,特异度为85.7%,与多普勒超声诊断仪测量PASP结果比较一致性较好(Kappa值=0.627)。结论血清Cav-1在COPD相关PAH患者表达明显下调,可以作为预测COPD相关PAH的新型血清标志物。

Objective To study the expression of serum caveolin-1(Cav-1) in patients with pulmonary hypertension(PAH) associated with chronic obstructive pulmonary disease(COPD), and to analyze its clinical significance.Methods According to whether combined with PAH, a total of 65 stable COPD patients were divided into COPD group [pulmonary systolic blood pressure(PASP) <40 mmHg, 35 cases] and COPD-PAH group(PASP ≥40 mmHg, 30 cases). Thirty healthy volunteers who received physical examination in our hospital during the same period were selected as normal control group.Baseline data, blood gas analysis, lung function indicators, and expression levels of Cav-1, IL-6, and TNF-α were compared. The receiver operating characteristic curve(ROC curve) was plotted and the optimal cut-off value for Cav-1 diagnosis of COPD combined with PAH was analyzed.Results The first second forced respiratory volume(FEV1)/forced vital capacity(FVC), FEV1 percentage of predicted value(FEV1%), and oxygen partial pressure [p(O2)] were lower in the COPD-PAH group and the COPD group than those in the control group, and the partial pressure of carbon dioxide [p(CO2)]and PASP were higher than those in the control group(P<0.01). The p(O2) was lower in the COPD-PAH group than that in the COPD group, and the p(CO2) and PASP were higher than those in the COPD group(P<0.01). The expression levels of Cav-1 were decreased gradually in the control group, COPD group and COPD-PAH group, while the expression levels of IL-6 and TNF-α were increased gradually(P<0.01). For predicting the risk of COPD combined with PAH, the area under the ROC curve was 0.902, the optimal cut-off value was 6.66 ng/ml with a sensitivity of 76.7% and a specificity of 85.7%. Cav-1 was consistent with the PASP results measured by Doppler ultrasound(Kappa value = 0.627).Conclusion The serumexpression of Cav-1 is down-regulated in the patients with PAH associated with COPD, and Cav-1 can be a novel serummarker for the diagnosis of PAH associated with COPD.