School of Basic Medical Sciences, Institute of Hypoxia Research, Cixi Biomedical Institute, Wenzhou Medical University, Wenzhou, China.
School of Basic Medical Sciences, Zhejiang University, Hangzhou, China.
Front Immunol. 2022 Aug 18;13:973108. doi: 10.3389/fimmu.2022.973108. eCollection 2022.
Chronic ethanol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). However, the mechanisms involved are unknown. One explanation is that ethanol produces damaging reactive oxygen species (ROS) and disturbs the balance of mitochondria within the lungs to promote a pro-injury environment. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate EtOH-LPS-induced lung injury. To test this, we investigated the effects of mitochondria-targeted ubiquinone, Mitoquinone (MitoQ) on ethanol-sensitized lung injury induced by LPS. Lung inflammation, ROS, mitochondria function, and mitophagy were assessed. We demonstrated that chronic ethanol feeding sensitized the lung to LPS-induced lung injury with significantly increased reactive oxygen species ROS level and mitochondrial injury as well as lung cellular NLRP3 inflammasome activation. These deleterious effects were attenuated by MitoQ administration in mice. The protective effects of MitoQ are associated with decreased cellular mitophagy and NLRP3 inflammasome activation and . Taken together, our results demonstrated that ethanol aggravated LPS-induced lung injury, and antioxidant MitoQ protects from EtOH-LPS-induced lung injury, probably through reducing mitophagy and protecting mitochondria, followed by NLRP3 inflammasome activation. These results will provide the prevention and treatment of ethanol intake effects with new ideas.
慢性乙醇滥用是一种全身性疾病，也是急性呼吸窘迫综合征（ARDS）和慢性阻塞性肺疾病（COPD）的一个危险因素。然而，其涉及的机制尚不清楚。一种解释是，乙醇产生有害的活性氧（ROS），并扰乱肺部线粒体的平衡，以促进促损伤环境。我们假设将抗氧化剂靶向线粒体将防止氧化损伤并减轻乙醇脂多糖（LPS）诱导的肺损伤。为了验证这一点，我们研究了靶向线粒体的泛醌，即 Mitoquinone（MitoQ）对 LPS 诱导的乙醇敏感肺损伤的影响。评估了肺炎症、ROS、线粒体功能和线粒体自噬。我们证明，慢性乙醇喂养使肺对 LPS 诱导的肺损伤敏感，ROS 水平和线粒体损伤以及肺细胞 NLRP3 炎性小体激活显著增加。MitoQ 给药可减轻这些有害作用。MitoQ 的保护作用与细胞线粒体自噬减少和 NLRP3 炎性小体激活减少有关。综上所述，我们的研究结果表明，乙醇加重了 LPS 诱导的肺损伤，抗氧化剂 MitoQ 可预防 EtOH-LPS 诱导的肺损伤，可能是通过减少线粒体自噬和保护线粒体，从而抑制 NLRP3 炎性小体的激活。这些结果将为预防和治疗乙醇摄入的影响提供新的思路。
