Melatonin protects against COPD by attenuating apoptosis and endoplasmic reticulum stress via upregulating SIRT1 expression in rats.

Abstract

The apoptosis of bronchial and alveolar epithelial cells plays a key role in chronic obstructive pulmonary disease (COPD). The endoplasmic reticulum (ER) stress induced by cigarette smoke contributes to apoptosis. Previous studies demonstrated that melatonin prevented the development of COPD. In addition, silent information regulator 1 (SIRT1) had a protective effect against COPD. However, it remains unclear whether SIRT1 is involved in the protection of melatonin against COPD. In this study, 32 male Wistar rats were randomly assigned to 4 groups: Control, COPD, COPD + Mel, and COPD + Mel + EX527. Rats were challenged with cigarette smoke and lipopolysaccharide with or without melatonin or EX527 (a selective inhibitor of SIRT1). The lung histopathology, apoptotic index, as well as the protein expressions of cleaved caspase-3, SIRT1, C/EBP homologous protein, and caspase-12 in the lung tissues were measured. These results demonstrated that melatonin attenuated apoptosis and ER stress in the lung tissues of rats with COPD. In addition, melatonin increased SIRT1 expression in lung tissues of rats with COPD, while inhibition of SIRT1 by EX527 upregulated ER stress and abolished the protective effect of melatonin against apoptosis. In conclusion, these findings suggested that melatonin protected against COPD by attenuating apoptosis and ER stress via upregulating SIRT1 expression in rats.