武汉云克隆科技股份有限公司

Abstract:

Background: Cigarette smoke exposure can trigger the activation of several processes such as oxidative stress, cellular senescence and autophagy. Preliminary data suggest that an acquired defect in autophagic processes may occur in the course of COPD.

Aims and objectives: Assuming that circulating Beclin1 levels may reflect the efficiency of autophagy process, we hypothesized that decreased circulating Beclin1 levels might be used to detect autophagy deficiency. Given that cellular senescence is involved in COPD pathophysiology and that autophagy defect may be a trigger of this process, we tested whether Beclin1 levels are linked to the reduction of telomere length, a hallmark of senescence.

Methods: Quantitative evaluation of Beclin1 protein level (ELISA Kit; E98557Hu, Uscn Life Science Inc., China) were performed in the sera of 280 subjects (non-smokers n=95, smokers n=93, COPD n=92) already well phenotyped with a special focus on ageing-related markers (Boyer, L. et al. PLoS One 2015 Mar 18;10(3)).

Results: Beclin1 protein level was correlated to age (R=-0.13; p Corr Pearson=0.027), FEV1 (R=0.12; p=0.039), telomere length (R=0.17; p=0.005) and appendicular skeletal muscle mass index (R=0.21; p=0.001). After adjustment for age, a statistically significant negative trend was found in serum Beclin1 protein level of non-smokers, smokers and COPD patients (2.31±0.23, 1.66±0.23 and 1.52±0.24 ng/ml, respectively; p=0.036).

Conclusions: Serum Beclin1 levels are decreased in COPD patients and are correlated with FEV1 and markers of accelerated ageing. These results support the hypothesis of a potential link between defective autophagy, senescence and COPD pathogenesis.

摘要：

背景：暴露在香烟雾中会导致氧化应激、细胞衰老、细胞自噬等。初步数据表明自噬过程中的缺陷可能伴随慢性阻塞性肺疾病的发生。

目的：如果Beclin1循环水平可以反映自噬效率，我们认为Beclin1循环水平降低可以用于检测自噬缺乏症。考虑到细胞衰老与COPD的病理生理学研究有关，自噬缺陷可能诱发细胞衰老，端粒长度作为细胞衰老的标志，我们测试了Beclin 1水平是否与端粒长度缩短有关。

方法：对带有老化相关标记（Boyer, L. et al. PLoS One 2015 Mar 18;10(3)）的280位受试者(其中不吸烟者95例，吸烟者93例，慢性阻塞性肺疾病患者92例)进行Beclin1蛋白水平的定量评价（ELISA Kit; E98557Hu, Uscn Life Science Inc., China）。

结果：Beclin1蛋白水平与年龄（R=-0.13; p Corr Pearson=0.027), FEV1 (R=0.12; p=0.039)，端粒长度 (R=0.17; p=0.005）和阑尾骨骼肌质量指数（R=0.21; p=0.001）有关。调整年龄层次后，不吸烟者、吸烟者和慢性阻塞性肺疾病患者的血清Beclin 1蛋白水平呈显著负相关趋势（分别为2.31±0.23, 1.66±0.23 and 1.52±0.24 ng/ml; p=0.036）。

结论：Beclin 1水平在COPD患者中降低，与FEV 1及加速老化指标相关。这些结果表明自噬缺陷、细胞衰老与COPD发病机制之间存在潜在联系。

使用试剂原文信息：Quantitative evaluation of Beclin1 protein level (ELISA Kit; E98557Hu, Uscn Life Science Inc., China) were performed in the sera of 280 subjects