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.

Objective : To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice． Methods : Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) . Results: Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group． Conclusion ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.