内质网应激(endoplasmic reticulum stress,ERS)下的未折叠蛋白反应(unfolded protein response,UPR)可调节脂质代谢,与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的进展有极大的相关性.当肝细胞在受到某些刺激,如缺氧或氧化应激时,会发生ERS,启动UPR以恢复细胞稳态.ERS又有急性ERS和慢性持续性ERS两种形式,急性ERS所触发的UPR是维持细胞稳态的重要反应机制,而慢性持续性ERS会启动细胞的凋亡程序,诱导细胞凋亡,与NAFLD的发生发展密切相关,其可能是NAFLD进程中的关键因素.本文回顾了 NAFLD进展与UPR的联系,从脂质代谢、自噬角度讨论了 UPR与NAFLD的关系,以期进一步深入了解NAFLD的发病机制,为NAFLD的预防和治疗提供指导.
Progress in investigating the role of unfolded protein response in the progression of non-alcoholic fatty liver disease
The unfolded protein response(UPR)under endoplasmic reticulum stress(ERS)is closely associated with the progression of non-alcoholic fatty liver disease(NAFLD).ERS occurs when hepatocytes are exposed to certain stimuli,such as hypoxia or oxidative stress,initiating the UPR to restore cellular homeostasis.There are two forms of ERS:Short-term ERS and long-term ERS.Short-term ERS,triggered by UPR,is an important response mechanism to maintain cell homeostasis,but long-term ERS will initiate cell apoptosis program,induce cell apoptosis,closely related to the development of NAFLD,it may be a key link in the process of NAFLD.We reviewed the association between the progression of NAFLD and UPR,and discussed how UPR promoted the pathogenesis of NAFLD mainly from the perspec-tive of lipid metabolism and autophagy.This review can deepen the understanding of the interaction between UPR and NAFLD,help us to have a deeper understanding of the pathogenesis of NAFLD,and provide guidance for the prevention and treatment of NAFLD.
Endoplasmic reticulum stressUnfolded protein responseNon-alcoholic fatty liver diseaseLipotoxicity
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