Nrf2调控的铁死亡途径在非酒精性脂肪性肝病防治中的作用机制

Role of Nrf2-regulated Ferroptosis Pathway in The Prevention and Treatment of Nonalcoholic Fatty Liver Disease

非酒精性脂肪性肝病(NAFLD)是发病率很高的慢性肝病类型,与肥胖、糖尿病、高脂血症等代谢综合征密切相关,是当前重要的公共健康问题之一。其具体的发病机制尚不清楚。目前有研究认为铁死亡参与了NAFLD的发生与发展,铁死亡是一种新型程序性细胞死亡。核因子E2相关因子2(Nrf2)是调控铁死亡过程中的重要核因子,对铁死亡过程中抗氧化、铁代谢以及脂质过氧化途径起到调控作用,并且已被报道可能通过抑制铁死亡改善NAFLD。本文通过对铁死亡与NAFLD的关系研究进行梳理,探究Nrf2调控铁死亡改善NAFLD的可能机制。最后,对存在的问题进行分析并提出未来研究展望。

Nonalcoholic fatty liver disease(NAFLD)is a chronic liver disease with high incidence.NAFLD is closely related to obesity,diabetes,hyperlipidemia and other metabolic syndromes,and it is one of the important public health problems at present.Its specific pathogenesis is still unclear.At present,some studies believe that ferroptosis is involved in the occurrence and development of NAFLD,and ferroptosis is a new type of programmed cell death.Nrf2 is an important nuclear factor in the regulation of ferroptosis.First of all,Nrf2 can directly or indirectly regulate the downstream antioxidant GPX4 to participate in ferroptosis and the development of NAFLD,and can stimulate FSP1 transcription or directly stimulate HO-1 and Sesn2 transcription to play an antioxidant role when GPX4 is inactivated.Secondly,iron overload is closely related to ferroptosis and NAFLD.Nrf2 may reduce ferroptosis caused by iron overload by controlling iron storage and iron output,and finally improve NAFLD.However,the current research focuses on Nrf2 regulating iron storage affecting NAFLD,while Nrf2 regulating iron output and affecting ferroptosis and NAFLD have not been reported.In addition,Nrf2 is expected to regulate lipid peroxidation and inhibit ferroptosis by directly affecting PPARγ or indirectly affecting AMPK.Finally,the study shows that activating Nrf2 may inhibit ferroptosis by regulating mitochondrial dysfunction.All in all,Nrf2 can participate in the occurrence and development of ferroptosis and NAFLD through many ways.It is hoped that more ways related to Nrf2 will be found in the future to help improve NAFLD.