Effects Of Jieduan-Niwan Formula On The JNK-induced Transcription Factor Pathway In Acute-on-Chronic Liver Failure Rats

Objective The aim of the present study was to observe the effects of the prescription of Jie Duan-Ni Wan on JNK signaling pathway protein expression in liver tissue of rats with Acute-on-Chronic Liver Failure(ACLF),and to investigate the relationship between the expression of JNK signaling pathway so as to elucidate the mechanism of its effect on hepatocellular apoptosis induced by ACLF in rats.The aim of this study is to provide feasible experimental data for the prevention and treatment of ACLF by using JieDuan-Ni Wan prescription.Method Seventy SPF Wistar male rats were randomly divided into normal control group,model group,truncated inverse group and JNK inhibitor SP600125 group.After being immunized with porcine serum,rats were induced to form hepatic fibrosis model,and then combined with D-Galactosamine / lipopolysaccharide(D-Gal N /LPS)to establish an ACLF rat model.The SP600125 group received intraperitoneal injection of SP600125 for half an hour before the acute challenge.Rats in each group were drawn at 4,8,and 12 h after acute challenge.The levels of c-Jun and Fas L protein were detected by immunohistochemistry,and the contents of Caspase3,Caspase8 and Fas were detected by immunohistochemistry.The expression of c-Jun and Fas L protein were detected by immunohistochemical method.Result1.No death during modeling.Compared with the control group,the diet and waterconsumption of the rats in the treatment group were lower than those in the control group.The weight in control group was not significantly different from the normal group.Acute attack,rat hair upright,body trembling,anti-capture ability weakened,unresponsive.The transthoracic group was less than the model group.2.Compared with the model group,ALT,AST and Tbi L of the model group were significantly increased(P <0.01),and compared with the model group,(P<0.01 or P<0.05),and the levels of serum ALT,AST and Tbi L were much lower in SP600125 group.3.Compared with the normal group,the PTA of the model group decreased significantly(P<0.01),and gradually decreased with the time.Compared with the corresponding time point model group,PTA increased in the truncated inverse group and SP600125 group,the difference was statistically significant(P<0.05)at 4h,8h,and there was no statistical difference at 12 h.4.Compared with the normal group,the TNF-? content in the model group increased at all time points,and the difference was statistically significant(P<0.05).Compared with the corresponding time point model group,the contents of 4h and 8h in SPP group and SP600125 group were significantly decreased(P<0.01),but there was no statistical difference at 12 h.5.The expression of Caspase3,Caspase8,Fas,c-Jun and Fas L protein in the model group was significantly higher than that in the normal group at 4h(P<0.05),reaching the peak at 8h and decreasing at 12 h.The expressions of Caspase3,Caspase8,Fas,c-Jun and Fas L were decreased at 4h and 8h in JDNW group and SP600125 group,the difference was statistically significant,but that in 12 h group was slightly higher than that in model group.6.There was no significant difference between the two groups in the JDNW group and the SP600125 group,and the mechanism of action may be similar.Conclusion1.By reduce the serum levels of ALT,AST,Tbi L and improve plasma PTA levels,JDNW prescription could improve liver function and coagulation function in ACLF rats;2.The levels of serum TNF-? in rats' serum,the expression of Caspase3,Caspase8,Fas,c-Jun and Fas L in liver tissue of ACLF rats can be inhibited by reducing the expression of hepatocellular carcinoma and slow down the process of hepatocyte apoptosis.The mechanism of action is similar to that of JNK inhibitor SP600125;3.Its mechanism was via the JNK signaling pathway mediated by the transcription factor pathway of apoptosis,thereby protecting liver function,inhibiting liver failure.