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外周血单个核细胞自噬水平与慢性阻塞性肺疾病患者临床参数的相关性。

Correlation between autophagy levels in peripheral blood mononuclear cells and clinical parameters in patients with chronic obstructive pulmonary disease.

机构信息

Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

出版信息

Mol Med Rep. 2018 Jun;17(6):8003-8009. doi: 10.3892/mmr.2018.8831. Epub 2018 Mar 29.

Abstract

Autophagy serves a role in the pathogenesis of chronic inflammatory diseases. The aim of the present study was to compare the autophagy levels in the peripheral blood mononuclear cells (PBMCs) of patients with chronic obstructive pulmonary disease (COPD) and healthy individuals and to assess the association between autophagy and the clinical parameters of COPD. Samples of peripheral blood from 20 patients with stable COPD and 20 healthy controls were collected. PBMCs were harvested using Ficoll density gradient centrifugation. Levels of the autophagy‑associated proteins ubiquitin‑binding protein p62 (p62), microtubule‑associated proteins 1A/1B light chain 3A (LC3I/II) and beclin‑1 in PBMCs were detected by western blotting. Enzyme‑linked immunosorbent assay kits were used to detect the serum concentrations of interleukin (IL)‑6, IL‑8 and tumor necrosis factor (TNF)‑α. Associations between the levels of autophagy and forced expiratory volume in 1 sec % predicted (FEV1%) and pro‑inflammatory factors were assessed. Western blotting demonstrated that the protein expression of p62 was decreased, but LC3II/I and beclin‑1 levels increased in patients with COPD compared with healthy controls. Serum levels of IL‑6, IL‑8 and TNF‑α were increased in patients with COPD. The extent of PBMC autophagy was negatively correlated with FEV1% predicted, but positively correlated with levels of pro‑inflammatory cytokines. The levels of autophagy in PBMCs in patients with COPD were increased and were negatively correlated with FEV1% predicted and positively correlated with circulating levels of pro‑inflammatory cytokines. Autophagy may serve a role as a biomarker of the severity of COPD or as a therapeutic target for treatment of COPD.

摘要

自噬在慢性炎症性疾病的发病机制中起作用。本研究旨在比较慢性阻塞性肺疾病(COPD)患者和健康个体外周血单个核细胞(PBMC)中的自噬水平,并评估自噬与 COPD 临床参数之间的相关性。收集 20 例稳定期 COPD 患者和 20 例健康对照者的外周血样本。使用 Ficoll 密度梯度离心法从 PBMC 中提取 PBMC。通过 Western blot 检测 PBMC 中自噬相关蛋白泛素结合蛋白 p62(p62)、微管相关蛋白 1A/1B 轻链 3A(LC3I/II)和 beclin-1 的水平。酶联免疫吸附试剂盒检测血清中白细胞介素(IL)-6、IL-8 和肿瘤坏死因子(TNF)-α的浓度。评估自噬水平与 1 秒用力呼气量占预计值百分比(FEV1%)和促炎因子之间的相关性。Western blot 结果表明,与健康对照组相比,COPD 患者的 p62 蛋白表达降低,LC3II/I 和 beclin-1 水平升高。COPD 患者的血清 IL-6、IL-8 和 TNF-α水平升高。PBMC 自噬程度与 FEV1%预测值呈负相关,与促炎细胞因子水平呈正相关。COPD 患者 PBMC 中的自噬水平增加,与 FEV1%预测值呈负相关,与循环中促炎细胞因子水平呈正相关。自噬可能作为 COPD 严重程度的生物标志物或作为 COPD 治疗的治疗靶点。

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