Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.
Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.
复制标题
槲皮素通过增强线粒体自噬减轻慢性乙醇引起的肝线粒体损伤
作者：
Yu X;Xu Y;Zhang S;Sun J;Liu P;Xiao L;Tang Y;Liu L;Yao P
新出现的证据表明，线粒体自噬激活减轻了乙醇诱导的肝损伤。然而，乙醇对线粒体自噬的影响并不一致。重要的是，对慢性乙醇消耗后线粒体自噬状态的了解是有限的。本研究评估了槲皮素（一种天然存在的类黄酮）对慢性乙醇诱导的线粒体损伤（主要是线粒体自噬）的影响。给予小鼠15周的乙醇（占总热量的30%），导致线粒体超微结构的改变、线粒体膜电位的丧失和膜脂成分的重塑，证明了线粒体损伤的显著性，槲皮素（100 mg/kg.bw）大大减轻了线粒体损伤。此外，槲皮素阻断了慢性乙醇诱导的线粒体自噬抑制，这体现在自噬体-溶酶体融合和线粒体自噬相关调控元件，包括LC3II、Parkin、p62和电压依赖性阴离子通道1 (VDAC1)，与FoxO3a核易位增加平行。在槲皮素介导的线粒体自噬激活中，amp活化蛋白激酶（AMPK）和细胞外信号调节激酶2 （ERK2）而不是AKT和Sirtuin 1参与。槲皮素通过增强线粒体自噬来减轻乙醇引起的线粒体损伤，强调了一种有前途的酒精性肝病预防策略。
Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.