Regulatory Mechanism Of Ytgan Capsule On TLR4/NF-kB Signal Pathway In Mice With Immune Liver Injury

Objective:The effect and mechanism of Yigan capsule on the TLR4/N F-kB signaling pathway in mice with immune liver injury were investigated in this experiment,which provided an experimental basis for the clinical treatment of immune liver injury by Yigan capsule.Methods:A total of 40 male mice were randomly divided into 5 groups:normal group,model group,Yigan capsule low,medium and high dose group.The Yigan capsule was administered by intragastric administration in low,medium and high dose groups once a day for 14 days.After 1 hours of the last administration,except the normal group,the mice in other groups were injected with concanavalin A into the tail vein to make an immune liver injury model.After ConA tail vein injection of 8h,the mice were harvested and the serum levels of ALT and AST were detected.The pathological changes of liver were observed by HE staining.The levels of IL-1 beta,IL-2 and IL-8 in serum were measured by enzyme immunoassay,and the expression of TLR4,MyD88,NF-kBP65 and Caspase-3 protein was detected by immunohistochemistry.Results:1.Compared with the normal group,the level of ALT and AST in the model group increased significantly(P<0.01).Compared with the model group,the level of ALT and AST in the high,middle and low dose groups of Yigan capsule decreased(P<0.01)in varying degrees(P<0.01),especially in the high dose group of Yigan capsule,which reduced the level of ALT and AST more obviously.2.In the model group,hepatocytes were balloonated,liver plate s were blurred,liver cells arranged in disorder,hepatic sinusoids w ere widened,inflammatory cells infiltrated,and focal necrosis occur red.Compared with the model group,the histopathological changes of liver tissues in the high,middle and low dose groups of Yigan ca psule were all improved in varying degrees.The arrangement of live r cells was more regular,the infiltration of inflammatory cells decre ased and the degeneration of hepatocytes was reduced.3.Compared with the normal group,the levels of serum IL-1,IL-2 and IL-8 increased in different degrees(P<0.01).Compared with the model group,the serum levels of IL-1 beta,IL-2 and IL-8 in the high,middle and low doses of Yigan capsule were significantly decreased(P<0.01),especially in the high dose group(P<0.01).4.Compared with the normal group,the expression of TLR4,My D88,NF-kBP65 and Caspase-3 in the liver tissue of the m odel group increased significantly(P<0.01).Compared with the model group,the expression of TLR4,MyD88,NF-kBP65 and C aspase-3 proteins in the liver tissues of the high,middle and lo w dosage groups of Yigan capsule decreased in varying degrees(P<0.01).Conclusion:1.Yigan capsule has been proved to be able to reduce liver damage in mice induced by concanavalin A,improve the pathol ogical changes of liver and play a therapeutic role in immune 1 aver injury.2.The levels of IL-1,IL-2 and IL-8 cytokines in the serum of mice with immune liver injury could be regulated by Yigan capsule.3.The expression of TLR4,MyD88,NF-kBP65 and Caspase-3 in liver tissues of mice with immune liver injury could be re gulated by Yigan capsule.In conclusion,Yigan capsule may regulate the levels of inf lammatory cytokines through the TLR4/NF-kB signaling pathway,thereby playing a therapeutic role in immune liver injury.