The Function And Mechanism Of P38? In Non-alcoholic Steatohepatitis

Recently,the incidence of nonalcoholic steatohepatitis(NASH)is increasing and has become the most common chronic liver disease in the world.Its pathogenesis has multiple strikes,such as insulin resistance,lipotoxicity damage and inflammatory response reaction.Mitogen activated protein kinase p38a plays an important role in JNK mediated inflammatory response and endoplasmic reticulum stress related oxidative stress.However,the role of p38a in nonalcoholic steatohepatitis is not clear,so the purpose of our study is to explore the function and clinical effects of p38a in nonalcoholic steatohepatitis.P38a?hep mice and its corresponding wild type mice were fed with methionine choline deficient(MCD)food for 4 weeks and fed with 45%high-fat diet(HFD)for 12 weeks.The primary hepatocytes from mice were isolated and tested in vitro.Wild type mice were fed with high cholesterol and high fat diet(HFHC)for 12 weeks,then p38 inhibitors were applied,followed by the detection of histology and biochemical indexes.First of all,in the MCD and HFD induced models,p38??hep mice showed more serious steatohepatitis.We further demonstrated that p38 deficiency was associated with the development of fatty liver by activating NF-?B/JNK pathway,inflammatory factors,oxidative stress and macrophage infiltration.Subsequently,co-culture system was used to explain the influence of hepatocytes on macrophage polarization.In the HFHC-induced model,p38 MAPK blocked the development of steatohepatitis.We demonstrate that p38a plays a key role in the pathogenesis of nonalcoholic steatohepatitis.Importantly,p38a plays a double role in the occurrence of NASH.On one hand,p38a inhibits the production of fatty liver in the initial stage of NASH;On the other hand,in the late stage of the disease,p38a maintains and promotes the development of nonalcoholic steatohepatitis.