Protective Role Of Esmolol On Acute Liver Injury In Septic Rats

Objective: To investigate the effect of esmolol on the liver function and the levels of inflammatory cytokines in liver tissue of septic rats and its possible mechanism.Methods: 48 SPF-Grade SD rats,male,were randomly divided into 3 groups,each with 16 rats.Including: sham operation(Sham)group,cecal ligation and puncture(CLP(NS))group,and esmolol intervention(CLP(ES))group.The Sham group: the cecum were only turned after opening the abdominal cavity,and the CLP(NS)group and CLP(ES)group were established rat models of sepsis by giving cecal ligation and puncture(CLP).In each group,the drug was pumped continuously through the internal jugular vein continue 6 hours.The CLP(ES)group was given 15mg/(kg·h)esmolol diluent,and the Sham group and CLP(NS)group were given the same volume of saline.and 8 rats were sacrificed at 6h and 24 h after successful modeling.At 6h and 24 h after operation,8 rats in each group were selected for blood collection under anesthesia,and liver tissues were collected and labeled after sacrifice.The serum levels of ALT and AST were detected by biochemical analyzer;the levels of IL-6 and HMGB-1 of rats liver tissue were detected by ELISA;the levels of protein expression of STAT3,pSTAT3(Tyr705),and SOCS3 in liver tissue were measured by Western Blot;HE staining were used to observe the pathological changes of liver tissue.Results: 1.Changes in liver function indicators: at 6h and 24 h after operation,the serum ALT and AST levels in the CLP(NS)and CLP(ES)groups were significantly higher vs.the Sham group,and reached a peak at 24 hours(P<0.05).The serum ALT and AST levels in the CLP(ES)group were lower vs.the CLP(NS)group at each time point(P<0.05).2.Changes of inflammatory cytokines in liver tissue: at 6h and 24 h after operation,The levels of IL-6 and HMGB-1 in liver tissue homogenate of rats in the CLP(NS)and CLP(ES)groups were significantly higher vs.the Sham group,and reached a peak at 24 hours(P <0.05).The degree of increase in the CLP(ES)group was lower vs.the CLP(NS)group at each time point(P<0.05).3.Marker protein expression in STAT3 signaling pathway in liver tissue: at6 h after operation,CLP(NS)group: the protein level of p-STAT3(Tyr705)was significantly higher than vs.the Sham group,the protein level of SOCS3 was significantly lower vs.the Sham group(P<0.05);CLP(ES)group: the protein level of p-STAT3(Tyr705)was lower vs.the CLP(NS)group,the protein level of SOCS3 was higher vs.the CLP(NS)group(P<0.05).at 24 h after operation,CLP(NS)group:the protein level of p-STAT3(Tyr705)was significantly higher vs.the Sham group,the protein level of SOCS3 was significantly lower vs.the Sham group(P<0.05);CLP(ES)group: the protein level of p-STAT3(Tyr705)was lower vs.the CLP(NS)group(P>0.05),the protein level of SOCS3 was higher vs.the CLP(NS)group(P>0.05).4.Pathological changes of liver tissue in rats: at 6h and 24 h after operation,Compared with the CLP(NS)group and the CLP(ES)group,the level of pathological damage of liver tissue was slight in the Sham group.There were inflammatory cells obvious infiltration,hepatocyte necrosis and vacuole degeneration can be seen in the CLP(NS)group.The level of pathological damage is the most serious in CLP(NS)groups,and 24 h group is more serious than 6h group.In the CLP(ES)groups,the level of pathological damage was significantly reduced vs.the CLP(NS)groups at each time point.Conclusion: When acute liver injury occurs in septic rats,esmolol can reduce the release of inflammatory cytokines,the degree of hepatocyte necrosis and inflammatory cells infiltration,and decrease the degree of acute liver injury.The possible mechanism are esmolol affects the release of inflammatory factors and exerts protective role in sepsis induced acute liver injury by the STAT3 signaling pathway.