Gu Chao, Li Yaqing, Xu Wu-Lin, Yan Jian-Ping, Xia Ying-jie, Ma Ying-Yu, Chen Chun, Wang Hui-Ju, Tao Hou-quan
a Department of Respiratory Medicine , Zhejiang Provincial People's Hospital , Hangzhou , Zhejiang , P.R. China.
COPD. 2015 Aug;12(4):444-52. doi: 10.3109/15412555.2014.974740.
In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.
在慢性阻塞性肺疾病（COPD）中，会出现两种主要的病理变化，即肺泡结构丧失和肺泡腔扩大。Ⅱ型肺泡上皮细胞（AECII）在维持肺泡稳态和肺组织修复中起着至关重要的作用。沉默调节蛋白1（SIRT1）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD(+)）的组蛋白脱乙酰酶，可调节包括炎症、凋亡、细胞衰老和应激抵抗在内的许多病理生理过程。本研究的主要目的是探讨SRT1720（一种SIRT1的药理学激活剂）是否能在体内保护暴露于香烟烟雾和气管内滴注脂多糖引起的肺气肿大鼠的AECII凋亡。在大鼠肺气肿诱导过程中，给予SRT1720可改善肺功能，包括气道阻力和肺动态顺应性。SRT1720治疗上调了表面活性蛋白（SP）A、表面活性蛋白C、SIRT1和叉头框O 3的水平，增加了SIRT1活性，下调了p53水平，并抑制了AECII凋亡。SRT1720治疗后，肺气肿引起的肺损伤得到缓解。SRT1720可保护肺气肿大鼠的AECII凋亡，因此可用于COPD的治疗。
