ATPR通过促进自噬缓解脂多糖诱导的小鼠急性肝损伤OACSTPCD

Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.