Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
Toxicol Appl Pharmacol. 2018 Oct 15;357:62-69. doi: 10.1016/j.taap.2018.08.019. Epub 2018 Aug 27.
Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality of liver disorders and a major health issue globally. ALD refers to a spectrum of liver pathologies ranging from steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Various mechanisms, including oxidative stress, protein and DNA modification, inflammation and impaired lipid metabolism, have been implicated in the pathogenesis of ALD. Further, reactive oxygen species (ROS) in particular, have been identified as a key component in the initiation and progression of ALD. Nuclear factor erythroid 2 like 2 (Nrf2) is a master regulator of the intracellular adaptive antioxidant response to oxidative stress, and aids in the detoxification of a variety of toxicants. Given its cytoprotective role, Nrf2 has been extensively studied as a therapeutic target for ALD. Paradoxically, however, emerging evidence have revealed that Nrf2 may be implicated in the progression of ALD. In this review, we summarize the role of Nrf2 in the development of ALD and discuss the underlying mechanisms. Clearly, more comprehensive studies with proper animal and cell models and in human are needed to verify the potential therapeutic role of Nrf2 in ALD.
酒精性肝病（ALD）是肝脏疾病发病率和死亡率的主要原因，也是全球主要的健康问题。ALD 是指一系列肝脏病理变化，包括脂肪变性、脂肪性肝炎、纤维化、肝硬化，甚至肝细胞癌。多种机制，包括氧化应激、蛋白质和 DNA 修饰、炎症和脂质代谢受损，都与 ALD 的发病机制有关。此外，活性氧（ROS）被特别确定为 ALD 起始和进展的关键组成部分。核因子红细胞 2 样 2（Nrf2）是细胞内对氧化应激的适应性抗氧化反应的主要调节剂，有助于多种毒物的解毒。鉴于其细胞保护作用，Nrf2 已被广泛研究作为 ALD 的治疗靶点。然而，矛盾的是，新出现的证据表明 Nrf2 可能与 ALD 的进展有关。在这篇综述中，我们总结了 Nrf2 在 ALD 发展中的作用，并讨论了潜在的机制。显然，需要进行更全面的研究，包括适当的动物和细胞模型以及人类研究，以验证 Nrf2 在 ALD 中的潜在治疗作用。
