OTUB1基因通过激活SLC7A11信号通路减轻对乙酰氨基酚诱导的急性肝损伤OA

Objective:To investigate the function and potential mechanism of OTU domain-containing ubiquitin aldehyde-binding protein 1(OTUB1)gene in acetaminophen(APAP)induced acute liver injury(ALI)and its potential mechanism.Methods:The signaling pathways related to ALI induced by APAP were studied by bioinformatics analysis,and the genes co-expressed with ferroptosis were screened out.Various doses(0,200,300,400 mg/kg)of APAP were intraperitoneally injected into BALB/c mice.The contents of enzymes and cytokines,liver coefficient,expression levels of OTUB1 and solute carrier family 7 member 11(SLC7A11)were detected.HE staining was used to observe the pathological changes of visceral tissues.Finally,OTUB1-overexpressing LO2 and QSG-7701 hepatocyte lines were constructed.The effects of OTUB1 overexpression on APAP-induced liver cell damage were analyzed by detecting cell viability,enzyme and cytokine contents,reactive oxygen species and mitochondrial membrane potential.Results:The results of bioinformatics showed that APAP-induced ALI and acute liver failure intersected with 12 ferroptosis genes,among which the OTUB1 gene,which was significantly downregulated in expression,was included.The results of animal experiments showed that APAP-induced ALI could cause inflammation in mice and down-regulate the expression of OTUB1 and SLC7A11 in a dose-dependent manner.The results of cell experiments showed that LO2 and QSG-7701 hepatocytes with overexpression of OTUB1 attenuate resist cellular inflammation,oxidative stress and mitochondrial damage caused by APAP.Conclusion:The OTUB1 gene may alleviate ALI induced by APAP by activating the SLC7A11 signaling pathway.