血清促血管生成和促纤维化因子与老年COPD患者肺功能降低和急性加重的关系-东南大学学报医学版

血清促血管生成和促纤维化因子与老年COPD患者肺功能降低和急性加重的关系

单位：西安交通大学医学院附属三二○一医院呼吸与危重症医学科, 陕西汉中 723000

分类号：R563

出版年·卷·期（页码）：2023·42·第四期（500-506）

摘要：

目的:探讨老年慢性阻塞性肺疾病(COPD)患者血清血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、成纤维细胞生长因子(FGF-2)和血小板衍化生长因子-AB(PDGF-AB)水平与肺功能及急性加重的关系。方法:选取2021年6月至2022年3月于本院就诊的118例老年稳定期COPD患者(稳定期COPD组)、130例急性加重期(AECOPD)患者(AECOPD组)和68例健康对照者(健康对照组),采集所有受试者空腹静脉血,使用Millipore多重蛋白分析仪检测血清中VEGF、TGF-β1、FGF-2和PDGF-AB水平,并对稳定期COPD患者进行肺功能检查。结果:COPD患者血清PDGF-AB、VEGF、FGF-2、TGF-β1水平较健康对照组显著升高,且AECOPD组血清FDGF-AB、FGF-2水平显著高于稳定期COPD组(P＜0.05)。对于稳定期COPD患者,血清PDGF-AB、VEGF、FGF-2、TGF-β1水平与疾病进展(包括GOLD分级、修正的医学研究委员会呼吸困难量表评分、COPD评估试验结果)呈正相关(P＜0.05),与肺一氧化碳弥散量(DLCO%prep)呈负相关(P＜0.05)。受试者工作特征曲线分析表明,血清PDGF-AB、VEGF、FGF-2、TGF-β1水平联合区分GOLD 3/4级COPD的曲线下面积为0.908(95%CI:0.853~0.963),灵敏度和特异度分别为83.3%和81.7%。结论:血清VEGF、TGF-β1、FGF-2和PDGF-AB水平升高与肺功能损害尤其是肺弥散功能降低相关,其有可能作为治疗COPD肺纤维化进展的潜在干预靶点。

Objective: To investigate the correlation between serum levels of vascular endothelial growth factor(VEGF), transforming growth factor β1(TGF- β1), fibroblast growth factor(FGF-2) and platelet diffractive growth factor-AB(PDGF-AB) with lung function and acute exacerbation of elderly chronic obstructive pulmonary disease(AECOPD) patients. Methods: From June 2021 to March 2022, 118 elderly patients with stable COPD, 130 patients with acute exacerbation(AECOPD) and 68 healthy controls were selected in our study. Fasting venous blood was collected from all subjects. The serum levels of VEGF, TGF-β1, FGF-2 and PDGF-AB were detected by Millipore multiplex protein analyzer. Pulmonary function tests were performed in patients with stable COPD. Results: The levels of serum PDGF-AB, VEGF, FGF-2 and TGF-1 in the COPD patients were significantly higher than the healthy control group, and the levels serum of FDGF-AB and FGF-2 in the AECOPD group were significantly higher than the stable COPD group(P<0.05). For patients with stable COPD, serum PDGF-AB, VEGF, FGF-2, TGF-1 levels were positively correlated with disease progression(including GOLD classification, modified Medical Research Council Dyspnea Scale score, and COPD assessment test results)(P<0.05), and these factors were negatively correlated with diffuse lung carbon monoxide(DLCO%prep)(P<0.05). Receiver operatingcharacteristic curve analysis showed that the area under the curve of PDGF-AB, VEGF, FGF-2 and TGF-1 combined to distinguish GOLD 3/4 COPD was 0.908(95%CI: 0.853-0.963), the sensitivity and specificity respectively were 83.3% and 81.7%. Conclusion: The elevated levels of serum VEGF, TGF-β1,FGF-2 and PDGF-AB are associated with the impairment of pulmonary function, especially the reduction of pulmonary diffusion function, which may be a potential intervention target for the treatment of pulmonary fibrosis progression in COPD.

参考文献：

[1] 王生伟.慢性阻塞性肺疾病急性加重患者生存期的影响因素分析[J].现代医学,2020,48(5):568-572.
[2] RAO W,WANG S,DULEBA M,et al.Regenerative metaplastic clones in COPD lung drive inflammation and fibrosis[J].Cell,2020,181(4):848-864.
[3] BARISIONE G,GARLASCHI A,OCCHIPINTI M,et al.Value of lung diffusing capacity for nitric oxide in systemic sclerosis[J].Physiol Rep,2019,7(13):e14149.
[4] 刘金良,庞军,李晓冬,等.慢性阻塞性肺疾病患者胸部定量CT参数与肺功能检测指标相关性分析[J].临床肺科杂志,2020,25(12):1831-1835.
[5] 来志龙,徐寒梅,赵万洲,等.特发性肺纤维化相关信号通路及治疗药物研究进展[J].药学进展,2022,46(7):535-544.
[6] LANDI C,CARLEO A,VANTAGGIATO L,et al.Common molecular pathways targeted by nintedanib in cancer and IPF:a bioinformatic study[J].Pulm Pharmacol Ther,2020,64:101941.
[7] CHANDA D,OTOUPALOVA E,SMITH S R,et al.Developmental pathways in the pathogenesis of lung fibrosis[J].Mol Aspects Med,2019,65:56-69.
[8] SAKORNSAKOLPAT P,PROKOPENKO D,LAMONTAGNE M,et al.Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations[J].Nat Genet,2019,51(3):494-505.
[9] BU T,WANG L F,YIN Y Q.How do innate immune cells contribute to airway remodeling in copd progression?[J].Int J Chron Obstruct Pulmon Dis,2020,15:107-116.
[10] LANGE P,AHMED E,LAHMAR Z M,et al.Natural history and mechanisms of COPD[J].Respirology,2021,26(4):298-321.
[11] POTO R,LOFFREDO S,PALESTRA F,et al.Angiogenesis,lymphangiogenesis,and inflammation in chronic obstructive pulmonary disease(COPD):few certainties and many outstanding questions[J].Cells,2022,11(10):1720.
[12] EGUCHI R,WAKABAYASHI I.HDGF enhances VEGF dependent angiogenesis and FGF-2 is a VEGF independent angiogenic factor in non small cell lung cancer[J].Oncol Rep,2020,44(1):14-28.
[13] CHIS A F,RÂJNOVEANU R M,MAN M A,et al.Increased vascular endothelial growth factor serum level and the role of 936C/T gene polymorphism in chronic obstructive pulmonary disease[J].Medicina,2021,57(12):1351.
[14] LADDHA A P,KULKARNI Y A.VEGF and FGF-2:promising targets for the treatment of respiratory disorders[J].Respir Med,2019,156:33-46.
[15] WANG L,XU Z,CHEN B,et al.The role of vascular endothelial growth factor in small-airway remodelling in a rat model of chronic obstructive pulmonary disease[J].Sci Rep,2017,7(1):1-9.
[16] ZANINI A,SPANEVELLO A,BARALDO S,et al.Decreased maturation of dendritic cells in the central airways of COPD patients is associated with VEGF,TGF-β and vascularity[J].Respiration,2014,87(3):234-242.
[17] 张钊,刘英宇,刘岩,等.硫氧环蛋白过氧化物酶-2对转化生长因子β1诱导的人胚肺成纤维细胞增殖及胶原合成的影响[J].中华劳动卫生职业病杂志,2020(1):7-12.
[18] HOÑKOVÁ L,UHLÍK J,BERÁNKOVÁ K,et al.Epithelial basement membrane thickening is related to TGF-beta 1 expression in children with chronic respiratory diseases[J].Pediatr Allergy Immunol,2014,25(6):593-599.
[19] ZOU W,HE F,LIU S,et al.PM2.5 induced the expression of fibrogenic mediators via HMGB1-RAGE signaling in human airway epithelial cells[J].Can Respir J,2018,2018:1817398.
[20] WANG J,LI Y,ZHAO P,et al.Exposure to air pollution exacerbates inflammation in rats with preexisting COPD[J].Mediators Inflamm,2020,2020:4260204.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录