Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, Kansas 66160-7417, USA.
Exp Biol Med (Maywood). 2010 May;235(5):547-60. doi: 10.1258/ebm.2009.009249.
Ethanol consumption causes fatty liver, which can lead to inflammation, fibrosis, cirrhosis and even liver cancer. The molecular mechanisms by which ethanol exerts its damaging effects are extensively studied, but not fully understood. It is now evident that nuclear receptors (NRs), including retinoid x receptor alpha and peroxisome proliferator-activated receptors, play key roles in the regulation of lipid homeostasis and inflammation during the pathogenesis of alcoholic liver disease (ALD). Given their pivotal roles in physiological processes, NRs represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases including ALD. This review summarizes the factors that contribute to ALD and the molecular mechanisms of ALD with a focus on the role of NRs.
乙醇摄入会导致脂肪肝,进而引发炎症、纤维化、肝硬化,甚至肝癌。目前广泛研究了乙醇发挥其损伤作用的分子机制,但尚未完全阐明。现在已经很明显,核受体(NRs),包括视黄酸 X 受体α和过氧化物酶体增殖物激活受体,在酒精性肝病(ALD)发病机制中对脂质稳态和炎症的调节起着关键作用。鉴于它们在生理过程中的关键作用,NRs 代表了治疗和预防包括 ALD 在内的多种代谢和脂质相关疾病的潜在治疗靶点。本综述总结了导致 ALD 的因素和 ALD 的分子机制,重点介绍了 NRs 的作用。