Resveratrol alleviates acute lung injury in mice by promoting Pink1/Parkin-related mitophagy and inhibiting NLRP3 inflammasome activation

作者：Dongdong Wu, Hui Zhang, Fang Li, Shuai Liu, Yang Wang, Zhao Zhang, Jiannan Wang, Qiuge Wu · 发表于：Biochimica et Biophysica Acta (BBA) - General Subjects · 年份：2024 · DOI：10.1016/j.bbagen.2024.130612 · 被引用次数：28 · 研究领域：Inflammasome and immune disorders、Autophagy in Disease and Therapy、Heme Oxygenase-1 and Carbon Monoxide

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by rapid onset and widespread inflammation in the lungs, often leading to respiratory failure. These conditions can be triggered by various factors, resulting in a severe inflammatory response within the lungs. Resveratrol, a polyphenolic compound found in grapes and peanuts, is renowned for its potent antioxidative and anti-inflammatory properties. In this study, we investigated how resveratrol protects against lipopolysaccharide (LPS)-induced ALI in mice. We established mouse models of LPS-induced ALI and inflammation in bronchoalveolar lavage fluid (BALF) macrophages. Through histopathological examination, immunofluorescence, western blot, enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM), we assessed the impact of resveratrol on the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes and the process of mitophagy. Our findings indicate that resveratrol significantly mitigated the lung injury and inflammation caused by LPS. This was achieved by inhibiting the oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the activation of NLRP3 inflammasomes. Resveratrol also reduced the levels of IL-1β and IL-18 in serum and BALF, decreased caspase-1 expression, and diminished macrophage pyroptosis. Furthermore, it upregulated Pink1, Parkin, Beclin-1, Autophag...