Effect Of Jianpi Yiqi Decoction On Pyroptosis-related Factors Of Hepatoma By Down-regulation Of Caspase-1 In Rats With DEN

Objective:This project was focused on the effect of Jianpi Yiqi decoction interfering with pyroptosis related factors through down-regulation of Caspase-1 expression in hepatoma,and the effects on liver function,inflammatory factors and the related pathway of pyroptosis of hepatoma.So diethylnitrosamine(DEN)induced the hepatocellular carcinoma model in rats was recruited in this study.Methods: 42 healthy male Sprague-Dawley rats were randomly divided into normal group(6 rats)and model group(36 rats),The hepatitiscirrhosis-liver cancer model was prepared by DEN according to 70mg/kg,once a week for 10 weeks.In the 16 th week of beginnning of modeling,the rats were randomly divided into 5 groups: the contrl group and the model group were intragastric administration with normal saline of 10.5g/kg,The different dose groups of TCM was received by 5.25 g / kg,10.5g / kg and21 g / kg Jianpi Yiqi decoction respectively,Casp1 inhibition group were injected VX-765 intraperitoneally at the dose of 4.5mg/kg/d,Once a day for4 weeks.The rats were sacrificed at the 0,6th,13 th and 20 th week respectively,After the blood was collected and the intact liver tissue was preserved and weighed.The liver pathological changes were observed under light microscopy.The activity of caspase-1 in Hepatocellular Carcinoma and the levels of serum alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(GGT),α-L-fucosidase(AFU),and were measured with biochemical method.ELISA was used to detect the levels of IL-1β,IL-18 and NFκB.Furthermore,the expression of Caspase-1,ASC,NLRP3 and GSDMD were detected by Western blot.Results:During DEN-induced hepatocarcinogenesis,the liver index of rats increased and the thymus index decreased gradually.Similarly,HE staining showed serious injury.The activity of caspase-1 in liver cancer tissue and the levels of serum ALT,AST,GGT,AFU,IL-1β,IL-18,NFκB increased gradually during hepatocarcinogenesis,including the protein expression of Caspse-1,ASC and NLRP3.Compared with the normal group,all were the highest in the 20 th week(P<0.01),Rats in the model group developed liver cancer at the 20 th week.After drug intervention,the activity of caspase-1 in liver cancer tissue,the levels of serum ALT,AST,GGT,AFU,IL-1β,IL-18,NFκB,and the protein expression of Caspse-1,NLRP3,ASC and GSDMD in the treated groups were decreased as compared with the model group(P<0.01),and the Casp1 inhibition group were the lowest in all experimental groups(P<0.01).Conclusion:Primary hepatocarcinoma rat model was successfully established with DEN.IL-1β,IL-18,NFκB and caspase-1 were symbolic inflammatory factors of hepatocyte damage during hepatocarcinogenesis,and may play important roles in the progress of hepatocarcinoma.Furthermore,the Jianpi Yiqi decoction may interfere with hepatocarcinoma by inhibiting the expression of IL-1β,II-18 and NFκB,liver tissue NLRP3,ASC,Caspase-1 protein.Provides a basis for further exploration and research into the related material of the drug of splenic fortification,which is effective in the future.