Study On The Effect Of High-dose Vitamin C On Liver Injury In Septic Mice

BackgroundSepsis is a complex clinical syndrome.It is a clinical syndrome in which the host’s response to infection is caused by many factors and develops into life-threatening organ dysfunction.The incidence of sepsis-related liver injury is high.The liver is the key organ that affects the survival of sepsis and one of the important objects attacked during sepsis.Early diagnosis and treatment of liver injury in sepsis can help to control the mortality of sepsis.In recent years,there have been debates about the efficacy of vitamin C in sepsis,and the mechanism and efficacy of high-dose vitamin C in treating liver injury caused by sepsis have not been determined.Therefore,this study intends to initially explore the effect of high-dose vitamin C on sepsis liver injury and its molecular mechanism by constructing the liver injury model of sepsis animal and cell level,and provide a new idea for the treatment of sepsis liver injury in clinical practice.MethodsThe model of sepsis liver injury in mice was established by cecal ligation and perforation(CLP).38 mice were randomly divided into sham operation group,CLP group,conventional dose vitamin C group,and high-dose vitamin C group according to whether they were given high-dose vitamin C treatment.One hour before CLP operation,the same volume of drugs were injected into the tail vein according to the grouping.After CLP operation,the temperature and body weight were monitored and the survival rate of 7 days in each group was counted.The liver and serum of mice were collected 24 hours after CLP,and the effects of high-dose vitamin C on liver injury in sepsis mice were detected by HE staining,TUNEL staining,ELISA,RT-PCR,Western Blot and transcriptome sequencing,and a cell model was established to initially explore the effect of high-dose vitamin C on liver injury in sepsis by regulating inflammatory reaction and cell death type at the cell level.Results(1)High dose of vitamin C can improve the survival rate of sepsis mice after CLP;(2)High-dose vitamin C reduces the inflammatory factor Tnf in the liver of septic mice-α、IL-6、IL-1β To improve liver injury in sepsis;(3)High dose of vitamin C can improve sepsis liver injury by reducing the level of P-MLKL,an executive protein of liver necrosis and apoptosis;(4)High dose of vitamin C can reduce liver injury in sepsis by inhibiting necrotic apoptosis of hepatocytes and macrophages.ConclusionOur experimental results show that high-dose vitamin C has protective effect on CLP-induced sepsis liver injury.High-dose vitamin C can improve liver injury in sepsis by reducing inflammation and inhibiting necrotic apoptosis.