Changes Of SOCS3 In The Pathogenesis Of Acute-on-chronic Liver Failure And Its Relationship With Inflammatory Factors

Objective:Acute-on-chronic liver failure(ACLF)is a serious disorder of liver function caused by acute injury factors on the basis of chronic liver disease,which is characterized by organ failure and high short-term mortality.Studies have shown that cytokine signal transduction inhibitor SOCS3 may be involved in the regulation of inflammatory response balance in liver failure.Therefore,exploring the role of SOCS3 in the pathogenesis of ACLF and its changes in the course of disease is conducive to the early warning of ACLF and provides ideas for the development of treatment.Methods:Healthy C57 mice were randomly divided into two groups.Mice in the control group were observed as a normal control group.Mice in the hepatic fibrosis group were injected intraperitoneally with 20%carbon tetrachloride(5ml/kg)once every 3 days for a total of 36 times.Mice in the acute-on-chronic liver failure group were injected intraperitoneally with 20%carbon tetrachloride(5ml/kg)once every 3 days for a total of 36 times.Three days after the last administration,the mice in the ACLF group were injected intraperitoneally with 20μg/kg LPS and 2g/kg D-gal.The blood and liver samples of mice in ACLF group were taken at 4h,8h,12h and 16h after injection,and the blood and liver samples of control group and hepatic fibrosis group were taken immediately after LPS and D-gal injection in ACLF group.Observe the liver function and pathological changes of mice.The expression of SOCS3 in liver was detected by real-time fluorescence quantitative PCR(qPCR),and the levels of inflammatory cytokines IL-33 and IFN-γ in peripheral blood and liver were detected by ELISA and qPCR,respectively.Results:The mouse model of acute-on-chronic liver failure was successfully established.In ACLF group,serum ALT and AST gradually increased and reached the highest value at 16h,CHE gradually decreased and decreased to the lowest value at 16h.IFN-γ in peripheral blood reached its peak 4 hours after LPS and D-gal were injected,IFN-γ in liver tissue reached its peak at 8h post-injection.The level of IL-33 in peripheral blood increased gradually after injection,and the increase was the most obvious at 16h.IL-33 in liver tissue began to increase at 4h,peaked at 12h post-injection,and then decreased gradually.The level of SOCS3 in liver tissue increased gradually after injection,peaked at 12h,and then decreased gradually.Correlation analysis showed that there was a strong linear correlation between SOCS3 in liver tissue and IL-33 in liver tissue of mice with acute-on-chronic liver failure,but there was no significant linear correlation between SOCS3 and IFN-γ in liver tissue.However,the peak of SOCS3 expression in liver tissue was later than IFN-γ in liver tissue,and there was also a certain correlation between them.Conclusion:The mouse model of acute-on-chronic liver failure was successfully established by CC14 combined with LPS and D-gal.The expression of SOCS3 in liver tissue of mice with acute-on-chronic liver failure increased with the increase of the degree of liver inflammation in the early stage.SOCS3 may be one of the early warning indicators for early diagnosis of acute-on-chronic liver failure.In addition,the expression of SOCS3 in liver tissue of acute-on-chronic liver failure is related to IFN-γ and IL-33,and its mechanism needs to be further studied.It is expected to provide new ideas for the development of the treatment of acute-on-chronic liver failure.