P62-Nrf2通路在非酒精性脂肪性肝炎中的作用

Role of P62-Nrf2 pathway in nonalcoholic steatohepatitis

非酒精性脂肪性肝病(NAFLD)是目前最常见的慢性肝病,大约有1/3的NAFLD患者会发展为非酒精性脂肪性肝炎(NASH)。多数学者认为,NASH的发病主要与肝脏脂肪异常积累和氧化应激等因素有关。核因子E2相关因子2(Nrf2)是细胞内抗氧化应激反应中的关键因子,而P62是一种多功能蛋白质,能够通过多种途径激活Nrf2。研究发现,抑制P62-Nrf2通路会加重肝脏脂肪变性、炎性反应和纤维化程度。而一些应用于其他疾病的药物,包括氯硝柳胺乙醇胺、依西替米等能够通过激活该通路抑制NASH的发生、发展。

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease currently,and about one-third of which will develop nonalcoholic steatohepatitis(NASH).Most scholars believe that the pathogenesis of NASH is mainly related to the abnormal accumulation of liver fat and oxidative stress.Nuclear factor E2-related factor 2(Nrf2)is a key factor in intracellular antioxidant stress response,and P62 is a multifunctional protein,which can activate Nrf2 through many ways.It is found that inhibition of P62-Nrf2 pathway could aggravate steatosis,inflammatory response and fibrosis of liver.It has been reported that some drugs used in other diseases,including niclosamide ethanolamine and ezetimibe,can inhibit the development of NASH by activating this pathway.