Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD
Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD
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DOI：
10.1016/j.intimp.2018.06.033
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发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
He, Baimei
中科院分区：
文献类型：
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作者：
Peng, Zhenyu;Zhang, Wenxuan;He, Baimei
慢性气道炎症是慢性阻塞性肺疾病（COPD）的一个特征。先前的研究表明，褪黑素对慢性阻塞性肺病有保护作用。此外，据报道，沉默信息调节因子1 （SIRT1）对COPD有益。然而，SIRT1是否参与褪黑素对COPD的保护作用尚不清楚。在本研究中，我们研究了褪黑素对COPD大鼠模型的影响，并探讨了其可能的机制。将28只雄性Wistar大鼠随机分为4组：对照组、COPD组、COPD + Mel组和COPD + Mel + EX527组。大鼠在有或没有褪黑激素或EX527的情况下被香烟烟雾和脂多糖（LPS）刺激28天。检测肺功能、肺组织病理学、炎症细胞计数、BALF中IL-1 β的浓度以及肺组织中SIRT1、NLRP3、cleaved caspase-1、ASC的蛋白表达。结果表明，褪黑素可以通过降低NLRP3炎性体和IL-1 β抑制气道炎症，从而阻止COPD的发展。此外，褪黑素增加了COPD大鼠肺组织中SIRT1的表达，而EX527抑制SIRT1则取消了褪黑素对COPD的保护作用。总之，这些发现表明，褪黑素通过SIRT1依赖性抑制NLRP3炎性体和IL-1 β来减轻COPD大鼠气道炎症。
Chronic airway inflammation is a characteristic feature of chronic obstructive pulmonary disease (COPD). Previous studies demonstrated that melatonin had a protective effect against COPD. In addition, silent information regulator 1 (SIRT1) was reported to be beneficial in COPD. However, whether SIRT1 is involved in the protective effect of melatonin against COPD remains unclear. In this study, we investigated the effect of melatonin on a rat model of COPD and explored the potential mechanisms. Twenty eight male Wistar rats were randomly assigned to four groups: control group, COPD group, COPD + Mel group and COPD + Mel + EX527 group. Rats were challenged with cigarette smoke and lipopolysaccharide (LPS) for 28 days with or without melatonin or EX527. The pulmonary function, lung histopathology, inflammatory cells count and the concentration of IL-1 beta in the BALF as well as the protein expressions of SIRT1, NLRP3, cleaved caspase-1 and ASC in the lung tissues were measured. The results demonstrated that melatonin prevented the development of COPD, which was attributed to the inhibition of airway inflammation by attenuating NLRP3 inflammasome and IL-1 beta. Furthermore, melatonin increased the expression of SIRT1 in lung tissues of rats with COPD, while inhibition of SIRT1 by EX527 abolished the protective effect of melatonin against COPD. In conclusion, these findings suggested that melatonin attenuated airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1 beta in rats with COPD.