Overview Of Molecular Mechanism Of Jiedu Huayu Granule In Prevention And Treatment Of Liver Failure And Experimental Study On Its Regulation Of JNK Signal Pathway

Objective: With the support of the project and based on literature research,to establish an animal model of acute liver failure(ALF),observe the intervention effect of Jiedu Huayu granule(JDHY)on hepatocyte regeneration in rats with acute liver failure,based on the JNK signaling pathway,some of the efficacy mechanisms of detoxification and stasis granules promoting liver regeneration and antagonizing liver failure were discussed.Methods: Fifty SPF SD rats,male,weighing 180-210 g,were fed adaptively for one week.The experimental rats were randomly divided into three groups:control group(Control),model group(Model)and Jiedu Huayu granule intervention group(JDHY),including 10 rats in the control group,20 rats in the model group and 20 rats in the Jiedu Huayu granule intervention group.Except the control group,all rats were injected with D-Gal N 600 mg / kg combined with LPS 20 ug / kg intraperitoneally.Traditional Chinese medicine began to be administered by gavage(Ig)72 hours before modeling,and continued to 72 hours after modeling,twice a day,with an interval of 12 hours.The model group was given the same amount of normal saline instead.72 h after the successful modeling,the abdominal aorta was dissected for blood,and the liver was dissected.The pathological changes of liver tissues in each group were observed after he staining.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and total bile acid(TBA)were detected by ELISA,the expression level of proliferating cell nuclear antigen(PCNA)protein was detected by immunohistochemistry(IHC),and the expression levels of JNK and c-jun m RNA in liver tissue were detected by RT-PCR,The expression levels of JNK1,JNK2,c-jun and p-JNK1,p-JNK2 and p-c-jun were detected by Western blot.Resu Lts:(1)HE staining: In the control group,the complete hepatic lobules can be seen under the microscope,the liver cells are arranged radially around the central vein,the hepatic cord is arranged in a regular and orderly manner,the hepatocytes are non-inflammatory infiltrates,degeneration and necrosis,and there is no cholestasis;the model group can see most of the liver lobular structure damaged under the microscope,the liver cord is not neatly arranged,a large number of inflammatory cell infiltrates can be seen in the liver tissue gap,a large number of dilated capillary bile ducts can be seen,hepatocytes are necrotic in large or sub-bulk forms,the necrosis rate is 70-80%,and only a small number of normal liver cells are seen In the Chinese medicine group,some liver lobular structures were damaged,the liver cords were not neatly arranged,accompanied by different degrees of hepatocyte swelling and degeneration,partially dilated capillary bile ducts could be seen,and different degrees of inflammatory cell infiltration and plaque/tablet necrosis could be seen in the portal vein area,and the necrosis rate was 40-50%,compared with the model group,the pathological damage in the Chinese medicine group was significantly reduced.(2)ELISA: Compared with control group,ALT,AST,TBIL and TBA in model and JDHY groups were significantly increased(P<0.05).Compared with model group,ALT,AST,TBIL and TBA in JDHY group decreased significantly(P<0.05).(3)IHC: Compared with control group,the expression of PCNA in model group decreased significantly(P<0.05),while that in JDHY group decreased(P>0.05).The expression of PCNA in JDHY group was significantly higher than that in model group(P<0.05).(4)RT-PCR: JNK and c-jun m RNA expression in the Model group were statistically significant(P<0.05)was significant compared with the Control group.JNK、c-jun m RNA expression in the JDHY group was decreased and the difference was not statistically significant(P>0.05).(5)Western blot: Compared with the control group,the contents of JNK1,JNK2 and c-jun protein in liver tissue in the model group increased with statistical significance(P<0.05),while the contents of JNK1 and c-jun protein in JDHY group increased with statistical significance(P<0.05),and the expression of JNK2 protein increased with no statistical significance(P>0.05).Compared with the model group,the protein contents of JNK1 and JNK2 in JDHY group decreased,the difference was statistically significant(P<0.05),and the protein content of c-jun decreased,the difference was not statistically significant(P>0.05).Compared with control group,the contents of p-JNK1,p-JNK2 and p-c-jun protein in liver tissue of model and JDHY groups were significantly higher(P<0.05).Compared with model group,the protein contents of p-JNK1,p-JNK2 and p-c-jun in JDHY group decreased significantly(P<0.05).Conclusions:(1)Jiedu Huayu granule may inactivate JNK / c-jun signal pathway by inhibiting JNK / c-jun phosphorylation,promote PCNA expression,enhance hepatocyte regeneration and antagonize liver failure(2)The scientific connotation of "removing blood stasis and generating new" of Jiedu Huayu granule in inhibiting inflammatory injury and promoting hepatocyte regeneration can promote the clinical application of traditional Chinese medicine in the prevention and treatment of liver failure.