Expression of nuclear factor erythroid-2-related factor 2, broad complex-tramtrack-bric a brac and Cap'n'collar homology 1 and γ-glutamic acid cysteine synthase in peripheral blood of patients with chronic obstructive pulmonary disease and its clinical significance

慢性阻塞性肺疾病患者外周血中核因子-E2相关因子2、广谱复合物-tramtrack-bric a brac、Cap'n'collar同源物1和γ-谷氨酸半胱氨酸合酶的表达及临床意义

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作者:Dongrong Li, Ding Sun, Yehan Zhu

Abstract

The purpose of the present study was to explore the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2)/BTB-CNC allogeneic 1 (Bach1)/γ-glutamic acid cysteine synthase (γ-GCS) and chronic obstructive pulmonary disease (COPD). The expression of Nrf2, Bach1, γ-GCS mRNA and protein in the peripheral blood mononuclear cells (PBMCs) of 80 COPD patients and 40 healthy volunteers were studied. Then, the correlation between Nrf2, Bach1, γ-GCS and lung function, inflammation and oxidative stress indicators was analyzed. Compared with healthy controls, Nrf2, Bach1 mRNA and protein levels were significantly increased in the PBMCs of COPD patients, while γ-GCS mRNA and protein levels were significantly decreased. Nrf2 and Bach1 protein levels in the nucleus were significantly elevated in acute exacerbation COPD patients compared with patients with a stable stage of COPD, while γ-GCS mRNA levels were significantly reduced. In addition, it was found that Nrf2 nuclear protein levels were significantly reduced in COPD patients compared with the control group, while Bach1 nuclear protein levels were significantly increased. Correlation analysis in COPD group demonstrated that γ-GCS mRNA was positively correlated with Nrf2 nuclear protein level, but negatively correlated with Bach1 nuclear protein level. Further analysis demonstrated that γ-GCS mRNA and Nrf2 protein in the nucleus was positively correlated with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)% and FEV1% predicted, and Bach1 protein in the nucleus was negatively correlated with FEV1/FVC% and FEV1% predicted. Additionally, the expression levels of Nrf2, Bach1 and γ-GCS were also associated with smoking. The expression of Nrf2, Bach1 and γ-GCS in peripheral blood mononuclear cells of patients with COPD was dysregulated and related to lung function, which provides a new basis for exploring further the pathogenesis of COPD.

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