NF-κB Mediated Activation Of Telomerase With Fluorofenidone Treatment For Chronic Liver Injury Induced By Diethylnitrosamine

Objective:To investigate the relationship between NF-κB mediated activation of telomerase on diethylnitrosamine-induced chronic liver injury in rats and the therapeutic effect of the fluorofenidone (AKF-PD).Methods:60male SD rats were randomly divided into normal control group (n=20), the DEN group (n=20) and AKF-PD treatment group (n=20). Rats in control group were given normal saline orally by10mg/kg according to body mass, rats in the DEN group were given0.2%DEN (0.975g/ml) solution orally by10mg/kg according to body mass, each group intragastrically5days a weeks for14weeks; AKF-PD treatment group intragastrically AKF-PD of500mg/kg according to body mass daily from the fifth week to the sixteenth week. Randomly selected3rats in each group in modeling5w,9w,13w and16w for2ml whole blood and hepatocyte extraction as well as portion of the right lobe of the liver tissue for:(1) biochemical assays:serum ALT and AST test;(2) liver histopathological examination:HE staining and Masson staining;(3) mRNA and protein expression of TERT, NF-κB and c-Myc in the liver tissue and hepatocytes.Results:(1) serum ALT in the DEN group was higher than in the control group in each sampling points, serum ALT in the AKF-PD treatment group were lower than the DEN group; Serum AST in the DEN group was higher than in the control group in each sampling points, serum AST in the AKF-PD treatment group were lower than the DEN group in the9th and16th week.(2) The liver inflammatory activity, collagen deposition and the extent of hepatocyte injury were improved in AKF-PD treatment group at each sample point than in the DEN group.(3) TERT mRNA expression and protein expression was significantly increased in hepatocytes in the DEN group; TERT mRNA expression and protein expression was significantly decreased in liver tissue but increased in hepatocytes in the AKF-PD treatment group compared with the DEN group.(4) NF-κB and c-Myc mRNA expression and protein expression were significantly increased in hepatocytes as well as NF-κB mRNA expression and protein expression in the liver tissue in DEN group; NF-κB and c-Myc mRNA expression and protein expression were reduced in hepatocytes as well as NF-κB mRNA expression and protein expression in the liver tissue in AKF-PD treatment group compared with the DEN group.Conclusions:(1) DEN successfully induced chronic liver injury;(2) AKF-PD may have therapeutic effect by reducing surum ALT and AST levels, improving liver tissue inflammatory from cell infiltration and protecting hepatocytes in chronic liver injury.(3) The function that AKF-PD can prevent damage of hepatocytes in chronic liver injury relates to the increase of TERT mRNA expression and protein expression in hepatocytes; the function that AKF-PD can delay the occurrence of inflammatory response in chronic liver injury may relate to the decrease of NF-κB and c-Myc mRNA expression and protein expression. Figure:15, table:15, reference:44...