2021 年第 8 期 第 16 卷

慢性阻塞性肺疾病急性加重期合并肺动脉高压患者血清核因子κB和Toll样受体4水平变化及意义

Changes and significances of serum nuclear factor-κB and Toll-like receptor 4 levels in patients with acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension

作者：刘蓓高苗张朋勃宋娟左秀萍

英文作者：Liu Bei Gao Miao Zhang Pengbo Song Juan Zuo Xiuping

单位：空军军医大学第一附属医院呼吸内科,西安710032

英文单位：Department of Respiratory Medicine the First Affiliated Hospital of Air Force Medical University Xi′an 710032 China

关键词：慢性阻塞性肺疾病急性加重期；肺动脉高压；核因子κB；Toll样受体4

英文关键词：Acuteexacerbationofchronicobstructivepulmonarydisease;Pulmonaryhypertension;Nuclearfactor-κB;Toll-likereceptor4

• 摘要：

• 目的 探讨慢性阻塞性肺疾病急性加重期（AECOPD）合并肺动脉高压（PH）患者血清核因子κB和Toll样受体4(TLR4)的水平变化及意义。方法 连续入选2018年11月至2020年3月于空军军医大学第一附属医院就诊的AECOPD患者127例，其中合并PH 49例(合并PH组)，未合并PH 78例（AECOPD组)。另选取同期体格检查健康的志愿者50名作为健康对照组。比较3组研究对象血清核因子κB和TLR4 mRNA的表达水平，肺功能指标和肺动脉收缩压（PASP）水平，分析合并PH组血清核因子κB mRNA与TLR4 mRNA表达水平的相关性，二者与肺功能指标和PASP的相关性，血清核因子κB和TLR4 mRNA对AECOPD合并PH的诊断效能。结果 AECOPD组和合并PH组血清核因子κB和TLR4 mRNA表达水平均高于健康对照组［(1.25±0.19)、（1.80±0.27）比（0.72±0.08），(1.09±0.15)、（1.50±0.23）比（0.65±0.09）］，且合并PH组二者表达水平均高于AECOPD组(均P<0.05)。AECOPD组和合并PH组第1秒用力呼气容积（FEV1）、用力肺活量（FVC）和FEV1/FVC水平均低于健康对照组，且合并PH组均低于AECOPD组；AECOPD组和合并PH组PASP均高于健康对照组，且合并PH组高于AECOPD组(均P<0.05)。合并PH组血清核因子κB mRNA与TLR4 mRNA表达呈正相关（r=0.573，P＜0.001），二者与FEV1、FVC、FEV1/FVC水平均呈负相关(r=-0.484、-0.469、-0.595，r=-0.428、-0.346、-0.530，均P＜0.001),而与PASP均呈正相关(r=0.568、0.507，均P<0.001)。二者联合检测诊断AECOPD合并PH的曲线下面积大于血清核因子κB和TLR4 mRNA单独检测(0.906比0.840、0.807，均P<0.05)。结论 血清核因子κB和TLR4在AECOPD合并PH患者中的表达明显下调，可作为AECOPD合并PH临床预防和针对性治疗的参考指标。

• Objective To investigate the changes and significances of serum nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR4) levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pulmonary hypertension (PH). Methods From November 2018 to March 2020, 127 AECOPD patients who were admitted to the First Affiliated Hospital of Air Force Medical University were consecutively enrolled. Among them, 49 patients were complicated with PH (complicated PH group) and 78 patients were not with PH (AECOPD group). In addition, 50 healthy volunteers who had physical examination during the same period were selected as healthy control group. The serum levels of NF-κB and TLR4 mRNA expression, pulmonary function indexes and pulmonary artery systolic pressure (PASP) levels were compared among the three groups. The correlation between the serum NF-κB mRNA and TLR4 mRNA expression levels, the correlation of the two indexes, pulmonary function indexes and PASP, and the diagnostic efficacy of serum NF-κB and TLR4 mRNA for AECOPD complicated with PH were analyzed. Results The serum levels of NF-κB and TLR4 mRNA expression in AECOPD group and complicated PH group were higher than those in healthy control group ［(1.25±0.19), (1.80±0.27) vs (0.72±0.08); (1.09±0.15), (1.50± 0.23) vs (0.65±0.09)］, and those in complicated PH group were higher than those in AECOPD group (all P<0.05). The forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and FEV1/FVC levels in AECOPD group and complicated PH group were lower than those in healthy control group, and those in complicated PH group were lower than those in AECOPD group; the PASP in AECOPD group and complicated PH group was higher than that in healthy control group, and that in complicated PH group was higher than that in AECOPD group (all P<0.05). Serum NF-κB mRNA and TLR4 mRNA expression were positively correlated in complicated PH group(r=0.573, P＜0.001), the two indexes were negatively correlated with FEV1, FVC and FEV1/FVC levels (r=-0.484, -0.469, -0.595, r=-0.428, -0.346, -0.530, all P<0.001), and were positively correlated with PASP (r=0.568, 0.507, both P<0.001). The area under the curve of the two combined detection of NF-κB and TLR4 mRNA in diagnosing AECOPD complicated with PH was larger than those alone (0.906 vs 0.840, 0.807, both P<0.05). Conclusion The expression of serum NF-κB and TLR4 are significantly down-regulated in patients of AECOPD complicated with PH, which can be used as reference indicators for clinical prevention and targeted treatment of AECOPD complicated with PH.