特发性肺纤维化患者血清热休克蛋白47和血管内皮生长因子的动态变化及其临床意义

Dynamic changes and clinical significance of serum heat shock protein 47 and vascular endothelial growth factor in patients with idiopathic pulmonary fibrosis

摘要:

目的 探讨特发性肺纤维化（IPF）患者血清热休克蛋白47（HSP47）和血管内皮生长因子（VEGF）的动态变化及其临床意义。方法 选取2017年1月—2019年8月天津市胸科医院收治的加重期IPF患者、稳定期IPF患者及同期该院体检的健康者共141例为研究对象，分别纳入加重期组、稳定期组及健康对照组，每组47例。采用酶联免疫吸附试验检测各组血清HSP47、VEGF水平及肺功能，采用高分辨率CT（HRCT）评分法评价各组肺纤维化程度，分析血清HSP47、VEGF、肺功能及HRCT评分之间的相关性。结果 加重期组、稳定期组及健康对照组的血清HSP47、VEGF水平比较，差异有统计学意义（P <0.05），加重期组血清HSP47、VEGF水平高于稳定期组，稳定期组高于健康对照组；加重期组动脉血二氧化碳分压（PaCO₂）、HRCT评分高于稳定期组（P <0.05）；加重期组动脉血氧分压（PaO₂）水平低于稳定期组（P <0.05）。加重期组第1秒用力呼气容积（FEV₁）、用力肺活量（FVC）、第1秒用力呼气容积占用力肺活量比值（FEV₁%）、一氧化碳弥散量占预计值百分比（DLCO%pred）低于稳定期组。Pearson相关性分析显示，HSP47与FEV₁、FVC、FEV₁%、DLCO%pred、PaO₂呈负相关（r =-0.735、-0.579、-0.612、-0.642和-0.636，均P <0.05），与PaCO₂、HRCT评分呈正相关（r =0.683和0.517，均P <0.05）；VEGF与FEV₁、FVC、FEV₁%、DLCO%pred、PaO₂呈负相关（r =-0.757、-0.583、-0.644、-0.656和-0.663，均P <0.05），与PaCO₂、HRCT评分呈正相关（r =0.597和0.525，均P <0.05）；HSP47与VEGF呈正相关（r =0.685，P<0.05）。结论 IPF患者血清HSP47、VEGF水平随着病情的加重而升高，检测血清HSP47、VEGF水平有利于辅助评估IPF患者的病情。

关键词:特发性肺纤维化;热休克蛋白47;血管内皮生长因子;肺功能;HRCT评分

Abstract:

Objective To explore the dynamic changes of serum HSP47 and VEGF in patients with idiopathic pulmonary fibrosis (IPF) and their clinical significance.Methods From January 2017 to August 2019, 47 patients with IPF in aggravating period (aggravating period group), 47 patients with IPF in stable period (stabilizing period group), and 47 healthy people (healthy control group), who were examined in our hospital in the same period, were selected as the study objects. Serum HSP47 and VEGF levels were determined with enzyme-linked immunosorbent assay (ELISA), and lung function in each group was measured, the degree of pulmonary fibrosis in each group was evaluated with high resolution CT (HRCT), and the correlation between the serum HSP47 and VEGF levels, pulmonary function, and HRCT score were analyzed.Results The levels of HSP47 and VEGF in healthy control group, stable group, and aggravating group were compared, the differences were statistically significant through analysis of variance (P < 0.05). The serum HSP47 and VEGF levels in the aggravating stage group were higher than those in the stable stage group, and those in the stable stage group were higher than those in the healthy control group, the differences were statistically significant (P < 0.05). The partial pressure of carbon dioxide in artery (PaCO₂) and HRCT score in the aggravating stage group were higher than those in the stable stage group, the differences were statistically significant (P < 0.05). The PaO₂ level in the aggravating group was lower than that in the stable group (P < 0.05). One second forced expiratory volume (FEV₁), forced vital capacity (FVC), one second forced expiratory volume to forced vital capacity ratio (FEV₁%), carbon monoxide diffusion volume as a percentage of the predicted value (DLCO% pred) in the aggravating period group were lower than those in the stable period group, the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that HSP47 were negatively correlated with FEV₁ (r = -0.735), FVC (r = -0.579), FEV₁% (r = -0.612), DLCO% pred (r = -0.642) and PaO₂ (r =-0.636) (P < 0.05), and positively correlated with the PaCO₂ (r = 0.683) and HRCT score (r = 0.517) (P < 0.05); VEGF were negatively correlated with FEV₁ (r = -0.757), FVC (r = -0.583), FEV₁% (r = -0.644), DLCO% pred (r = -0.656), and PaO₂ (r = -0.663) (P < 0.05), and positively correlated with the PaCO₂ (r = 0.597) and HRCT score (r = 0.525) (P < 0.05); HSP47 was positively correlated with VEGF (r =0.685, P < 0.05).Conclusion Serum HSP47 and VEGF in patients with IPF increased with the aggravation of the condition, and the detection of serum HSP47 and VEGF levels is helpful to assist in the assessment of the condition of patients with IPF.

Key words:idiopathic pulmonary fibrosis;HSP47 heat-shock proteins;vascular endothelial growth factors;respiratory function tests;HRCT score