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慢性阻塞性肺疾病加重期炎症发生的分子机制。

Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease.

机构信息

Servicio de Neumología, Hospital Universitario Son Dureta, Palma de Mallorca, Spain.

出版信息

Arch Bronconeumol. 2011 Apr;47(4):176-83. doi: 10.1016/j.arbres.2010.12.003. Epub 2011 Mar 31.

DOI:10.1016/j.arbres.2010.12.003
PMID:21454005
Abstract

INTRODUCTION

Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by an inflammatory and systemic response that persists for some time after their clinical resolution. The mechanisms of this inflammatory process are not well known.

OBJECTIVES

To explore the inflammatory changes and possible mechanisms during COPD exacerbation.

METHODS

We determined the inflammatory cell concentrations in blood and sputum, nitric oxide in exhaled air (FeNO), C-reactive protein (CRP) in plasma, cytokines (IL-6, 8, 1β, 10, 12, TNF-α) and SLPI (leukocyte protease inhibitor) and total antioxidant status (TAS) in blood and sputum, the activity of nuclear kappa B factor (NF-κ B) and of the histone deacetylase enzyme (HDAC) in 17 patients during COPD exacerbation and in stable phase, as well as in 17 smoker and 11 non-smoker controls.

RESULTS

COPD exacerbations are characterised by high levels of FeNO (p<0.05), plasma CRP (p<0.001) and IL-8, IL-1B, IL-10 in sputum (p<0.05) greater activation of NF-κ appaB in sputum macrophages compared with stable COPD and controls. During the stable phase, there continue to be high levels of oxidative stress, SLPI, IL-8, IL-6 and TNF-alfa, with no observed changes in either HDAC activity or in the amount of neutrophils in sputum, despite presenting a significant improvement (p<0.05) in lung function.

CONCLUSIONS

Changes were observed in different pulmonary and systemic inflammatory markers during COPD exacerbation, which did not completely resolve during stable phase. However, current treatment does not allow for HDAC activity to be modified, which limits its anti-inflammatory effects.

摘要

简介

慢性阻塞性肺疾病(COPD)的加重期以炎症和全身性反应为特征,其临床缓解后仍持续一段时间。这种炎症过程的机制尚不清楚。

目的

探讨 COPD 加重期的炎症变化及可能的机制。

方法

我们测定了血液和痰中的炎症细胞浓度、呼出气中的一氧化氮(FeNO)、血浆中的 C 反应蛋白(CRP)、细胞因子(IL-6、8、1β、10、12、TNF-α)和 SLPI(白细胞蛋白酶抑制剂)以及血液和痰中的总抗氧化状态(TAS),17 例 COPD 加重期和稳定期患者、17 例吸烟者和 11 例非吸烟者的核因子-κB 因子(NF-κB)和组蛋白去乙酰化酶(HDAC)活性。

结果

COPD 加重期的特点是 FeNO 水平升高(p<0.05)、血浆 CRP 水平升高(p<0.001)、痰中 IL-8、IL-1β、IL-10 水平升高(p<0.05),与稳定期 COPD 及对照组相比,痰巨噬细胞中 NF-κB 的活性明显升高。在稳定期,仍存在高水平的氧化应激、SLPI、IL-8、IL-6 和 TNF-alfa,尽管肺功能明显改善(p<0.05),但 HDAC 活性或痰中中性粒细胞数量无变化。

结论

在 COPD 加重期观察到不同的肺和全身炎症标志物发生变化,在稳定期未完全缓解。然而,目前的治疗方法不能改变 HDAC 活性,限制了其抗炎作用。

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