Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi, Italy.
Department of Medicine and Health Sciences, University of Molise, Via Francesco De Sanctis, 86100 Campobasso, Italy.
Oxid Med Cell Longev. 2018 May 9;2018:9391261. doi: 10.1155/2018/9391261. eCollection 2018.
Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease.
We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS).
The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC.
These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD.
氧化应激是慢性阻塞性肺疾病（COPD）的一种公认的致病机制。NAD 依赖性去乙酰化酶 Sirtuin 1（SIRT1）的表达已经被描述为减少，SIRT1 是一种抗衰老分子，在氧化应激反应中起着关键作用，在 COPD 患者的肺部。迄今为止，尚无研究调查全身性 SIRT1 活性是否与这种疾病的肺功能下降有关。
我们测量了 25 例 COPD 患者、20 名健康非吸烟者（HnS）和 20 名健康吸烟者（HS）的外周血单核细胞（PBMCs）中的 SIRT1 蛋白表达和活性以及血浆中的总氧化状态（TOS）、总抗氧化能力（TEAC）和氧化应激指数（TOS/TEAC）。
与对照组相比，COPD 患者的 SIRT1 活性显著降低，而蛋白表达逐渐降低（HnS>HS>COPD）。HnS 中的 TOS 水平明显低于与吸烟相关的受试者（COPD 和 HS），而 TEAC 水平则逐渐降低（HnS>HS>COPD）。在 COPD 患者中，SIRT1 活性，但不是蛋白水平，与肺功能参数（FEV1/FVC 和 FEV1）和 TEAC 显著相关。
这些发现表明 SIRT1 驱动的抗氧化活性的丧失在 COPD 发病机制中具有重要意义，并确定 SIRT1 活性作为识别轻度/中度、稳定 COPD 的潜在方便生物标志物。
