COPD患者血清炎症细胞因子水平与肺动脉压力的相关性

Correlation between serum inflammatory cytokines and pulmonary artery pressure in patients with chronic obstructive pulmonary disease

目的分析慢性阻塞性肺疾病(COPD)患者血清高迁移率族蛋白B1(HMGB1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、骨桥蛋白(OPN)和低氧诱导因子1α(HIF-1α)水平与肺动脉压力的相关性。方法本研究为队列研究。采用非随机抽样法,选取2020年1月至2022年5月湖南省永州市中心医院收治的105例COPD患者作为研究对象。根据COPD患者是否合并肺动脉高压分为肺动脉高压组45例和非肺动脉高压组60例。比较2组间血清HMGB1、IL-6、TNF-α、OPN和HIF-1α水平,观察2组间肺动脉压和肺功能指标[第1秒用力呼气容积/用力肺活量(FEV_(1)/FVC)、第1秒用力呼气容积占预计值百分比(FEV_(1)%pred)],分析不同肺动脉高压严重程度患者血清HMGB1、IL-6、TNF-α、OPN和HIF-1α水平。采用Pearson相关性分析血清HMGB1、IL-6、TNF-α、OPN、HIF-1α与肺动脉压、肺功能指标的相关性。结果肺动脉高压组HMGB1、IL-6、TNF-α、OPN和HIF-1α均高于非肺动脉高压组(t值分别为7.67、4.94、17.29、17.55、15.23,P值均<0.01)。肺动脉高压组肺动脉压高于非肺动脉高压组(t=16.06,P<0.01),FEV_(1)/FVC、FEV_(1)%pred均低于非肺动脉高压组(t值分别为9.94、11.61,P值均<0.01)。肺动脉高压组45例患者中轻度肺动脉高压20例,中度肺动脉高压15例,重度肺动脉高压10例。轻度肺动脉高压患者HMGB1、IL-6、TNF-α、OPN和HIF-1α均低于中度和重度肺动脉高压患者,中度肺动脉高压患者HMGB1、IL-6、TNF-α、OPN和HIF-1α均低于重度肺动脉高压患者,差异均有统计学意义(F值分别为47.36、25.93、138.83、33.34、30.77,P值均<0.01)。Pearson相关性分析结果显示,HMGB1、IL-6、TNF-α、OPN、HIF-1α与肺动脉压均呈正相关(r值分别为0.73、0.55、0.75、0.80、0.81,P值均<0.01),与FEV_(1)/FVC均呈负相关(r值分别为-0.87、-0.77、-0.81、-0.66、-0.82,P值均<0.01),与FEV_(1)%pred均呈负相关(r值分别为-0.91、-0.86、-0.84、-0.68、-0.85,P值均<0.01)。结论血清HMGB1、IL-6、TNF-α、OPN、HIF-1α与COPD患者肺动脉压力有关,可作为评估COPD合并肺动脉高压的重要指标。

Objective To investigate the relationship between pulmonary artery pressure and high mobility group protein B1(HMGB1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),osteopontin(OPN),and hypoxia inducible factor-1α(HIF-1α)levels in patients with chronic obstructive pulmonary disease(COPD).Methods This was a cohort study.Using a non-random sampling method,a total of 105 COPD patients admitted to Yongzhou Central Hospital of Hunan Province from January 2020 to May 2022 were selected as the research subjects.According to whether patients with COPD complicated with pulmonary hypertension were divided into pulmonary hypertension group(45 cases)and non-pulmonary hypertension group(60 cases).The serum levels of HMGB1,IL-6,TNF-α,OPN,and HIF-1α were compared between the two groups,and pulmonary artery pressure and pulmonary function indexes between the two groups were observed[forced expiratory volume in the first second/forced vital capacity(FEV_(1)/FVC)and forced expiratory volume in the first second as a percentage of expected value(FEV_(1)% pred)].Serum levels of HMGB1,IL-6,TNF-α,OPN,and HIF-1α in patients with different severity of pulmonary hypertension were analyzed.Pearson correlation analysis was used to analyze the correlation between serum HMGB1,IL-6,TNF-α,OPN,HIF-1α,and pulmonary artery pressure and lung function indexes.Results HMGB1,IL-6,TNF-α,OPN,and HIF-1α in the pulmonary hypertension group were significantly higher than those in the non-pulmonary hypertension group(t values were 7.67,4.94,17.29,17.55,and 15.23,respectively,all P<0.01).The pulmonary arterial pressure in pulmonary hypertension group was higher than that in non-pulmonary hypertension group(t=16.06,P<0.01),FEV_(1)/FVC and FEV_(1)% pred were lower than those in non-pulmonary hypertension group(t values were 9.94 and 11.61,respectively,both P<0.01).In the pulmonary hypertension group,20 patients had mild pulmonary hypertension,15 had moderate pulmonary hypertension,and 10 had severe pulmonary hypertension.HMGB1,IL-6,TNF-α,OPN,and HIF-1α in patients with mild pulmonary hypertension were lower than those in patients with moderate and severe pulmonary hypertension.HMGB1,IL-6,TNF-α,OPN,and HIF-1α in patients with moderate pulmonary hypertension were lower than those in patients with severe pulmonary hypertension.The differences were statistically significant(F values were 47.36,25.93,138.83,33.34,and 30.77,respectively,all P<0.01).Pearson correlation analysis showed that HMGB1,IL-6,TNF-α,OPN,and HIF-1α were positively correlated with pulmonary artery pressure(r values were 0.73,0.55,0.75,0.80,and 0.81,respectively,all P<0.01),negatively correlated with FEV_(1)/FVC(r values were-0.87,-0.77,-0.81,-0.66,and-0.82,respectively,all P<0.01),and negatively correlated with FEV_(1)% pred(r values were-0.91,-0.86,-0.84,-0.68,and-0.85,respectively,all P<0.01).Conclusions Serum HMGB1,IL-6,TNF-α,OPN,and HIF-1α are related to pulmonary arterial pressure in COPD patients,which can be used as an important indicator to evaluate COPD combined with pulmonary arterial hypertension.