Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China; Emergency Medicine and Difficult Diseases Institute, Central South University, Changsha 410011, China.
Clinical Nursing Teaching and Research Section, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Int Immunopharmacol. 2018 Sep;62:23-28. doi: 10.1016/j.intimp.2018.06.033. Epub 2018 Jun 30.
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-1β 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-1β. 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-1β in rats with COPD.
慢性气道炎症是慢性阻塞性肺疾病（COPD）的特征性表现。先前的研究表明褪黑素对 COPD 具有保护作用。此外，沉默信息调节因子 1（SIRT1）被报道对 COPD 有益。然而，SIRT1 是否参与褪黑素对 COPD 的保护作用尚不清楚。在这项研究中，我们研究了褪黑素对 COPD 大鼠模型的影响，并探讨了其潜在机制。28 只雄性 Wistar 大鼠随机分为四组：对照组、COPD 组、COPD+Mel 组和 COPD+Mel+EX527 组。大鼠接受香烟烟雾和脂多糖（LPS）处理 28 天，同时给予或不给予褪黑素或 EX527。测量肺功能、肺组织病理学、炎症细胞计数和 BALF 中 IL-1β的浓度以及肺组织中 SIRT1、NLRP3、cleaved caspase-1 和 ASC 的蛋白表达。结果表明，褪黑素预防了 COPD 的发展，这归因于通过减轻 NLRP3 炎症小体和 IL-1β抑制气道炎症。此外，褪黑素增加了 COPD 大鼠肺组织中 SIRT1 的表达，而 EX527 抑制 SIRT1 则消除了褪黑素对 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 炎症小体和 IL-1β减轻了 COPD 大鼠的气道炎症。
