RÉSUMÉ
Objective @# To investigate the effects of milk derived pentapeptide prolin⁃glycine⁃proline⁃isoleucine⁃pro⁃ line ( PGPIP) on chronic alcoholic liver injury in mice and its related molecular mechanism . @*Methods @#Forty C57BL/6 mice were randomly divided into control group , model group , glutathione(GSH) group , PGPIPN group .The mice model of chronic alcoholic fatty liver was established by 10 d ad libitum oral feeding with the Lieber⁃DeCarli(LD) ethanol liquid diet plus one binge . Drug intervention was given at the same time . Based on the reported RNA sequencing data in gene expression omnibus (GEO) database , the differential expression of liver endoplasmic reticulum stress⁃related genes was analyzed by cluster heat map . Liver hematoxylin⁃eosin (HE) staining was used to analyze the pathological effects of each treatment group on alcoholic liver injury in mice . Oiled Red O staining was used to analyze the effects of each treatment group on the accumulation of liver lipid droplets in mice . Transtransduction protein expression was detected by Western blot . @*Results @#The pathological examination of PGPIP group was similar to that of Control group , and the liver injury of mice was significantly reduced . The accumulation of lipid droplets in the liver of mice in the model group was manifested as mixed lipid droplets of different sizes , and PGPIP treatment significantly reduced the accumulation of liver lipid droplets induced by alcohol . PGPIP had significant effects on the PERK⁃eIF2α⁃ATF4 pathway and the expression of transcriptional activator 6 ( ATF6 ), Cleaved Caspase 3 protein . @*Conclusion @#Pentapeptide PGPIP can alleviate chronic alcoholic fatty liver and liver injury in mice . The mechanism may be attributed to reducing the accumulation of lipid droplets in hepatocytes , en⁃ doplasmic reticulum stress , and hepatocyte apoptosis .