Study On The Mechanism Of Jiedu Huayu Granule Antagonizing ACLF In Rats From The Perspective Of Regulating Th17 Related Inflammatory Factors

Objective:To observe the effects of Jiedu Huayu Granule on the general condition,body weight,liver function,liver histopathological changes and the contents of serum interleukin-17（IL-17）,interleukin-17A（IL-17A）and interleukin-23（IL-23）inflammatory factors in rats with chronic acute liver failure（ACLF）,To explore the mechanism of Jiedu Huayu granule antagonizing ACLF in rats from the perspective of immune inflammation.Methods:After the adaptive feeding of 40 SPF grade SD rats for 1 week,Forty SPF grade SD rats,male,220g±10g,Randomized into 3 groups,10 in normal group（Normal）,15 in model group（Model）,15 in Chinese medicine group（JDHY）,Except for the normal group,Model group:40%carbon tetrachloride（CCl4）:olive oil=4:6,With an intraperitoneal injection at 2.0 ml/Kg,Two times a week,A rat model of liver cirrhosis was established for 10 weeks,The rat ACLF model was then induced by disposable intraperitoneal injection of 400mg·kg^-1D-amino galactose（D-galactosamine D-Ga LN）and 10μg·kg^-1lipopolysaccharide（Lipopolysaccharide LPS）,Gavage was started 5 days before the acute attack with D-Gal N and LPS,In the traditional Chinese medicine group,The model group gave equal amounts of distilled water for control,During the general condition,weight change,death,urine and feces of rats,Three groups of rats were killed at 48h after successful moulding,Liver collection by blood collection and dissection from the abdominal aorta,Pathpathology of rat liver was observed after HE staining,The serum levels of glutamate aminotransferase（Alanine aminotransferase ALT）,aspartate transferase（aspartic transaminase AST）,total bilirubin（total bilirubin TBi L）,Serum IL-17,IL-17A,and IL-23 content were measured by the ELISA kit.result:（1）General condition:during 1 week of adaptive feeding,the rats in the three groups were in good mental condition,bright hair color,Normal组diet and Normal defecation.During the injection of CCl₄olive oil,the activity of rats in the model group and traditional Chinese medicine group decreased,the luster of hair color decreased,and the diet gradually decreased.At the end of the 10th week,the abdomen of rats swelled,the ascites was obvious,the stool was rotten and partially shapeless,and the urine color became darker;After intraperitoneal injection of D-Gal N and LPS,the rats in the model group were depressed,liked to curl up,had dark yellow and matte hair,did not like eating,had rotten stools and dark yellow urination.After intervention,compared with the rats in the model group,the rats in the traditional Chinese medicine group had increased activities,ate more,some of their stools could be formed,and their urination was light yellow,which was generally improved compared with the model group.（2）Comparison of survival rate of rats in each group:all rats in the Normal group survived,15 rats in the model group and 15 rats in the traditional Chinese medicine group.After 48 hours of acute attack on the basis of liver cirrhosis,there were 8 rats in the final model group,with a survival rate of 53.3%,which was similar to the literature^[1].There were9 rats in the traditional Chinese medicine group,with a survival rate of60%.（3）The weight changes of rats in each group:there was no significant difference among the Normal group,model group and traditional Chinese medicine group before the experiment（P>0.05）;After the experiment,the weight gain of rats in the model group and traditional Chinese medicine group was significantly lower than that in the Normal group（P<0.05）.There was no significant difference between the traditional Chinese medicine group and the model group（P>0.05）.（4）Comparison of liver histopathology of rats in each group:under HE staining,the hepatocytes in the Normal group were arranged orderly,the structure of hepatic lobules was clear,the hepatocytes were arranged radially with the central vein as the center,no obvious edema and necrosis,no inflammatory cell infiltration and no fibrous tissue proliferation were found;In the liver tissue of cirrhotic rats,the structure of Normal hepatic lobules can be destroyed,and a large number of proliferative fibrous tissues divide and wrap the regenerative nodules of hepatocytes into round like hepatocyte clusters of different sizes.Obvious pseudolobules are formed,the arrangement of hepatocytes in pseudolobules is disordered,and hepatocyte edema,necrosis and regeneration can be seen;In the model group,hepatocytes showed massive necrosis,enlarged nuclei,binuclear and polynuclear atypia,massive infiltration of inflammatory cells,unclear structure of hepatic lobules,dilation and congestion of hepatic sinuses,and obvious edema of residual hepatocytes;Compared with the model group,the necrotic area of hepatocytes,inflammatory cell infiltration,cell swelling and necrosis in the traditional Chinese medicine group were significantly reduced.（5）Comparison of alt,AST and TBi L in serum liver function of rats in each group:compared with the Normal group,alt,AST and TBi L in model group and traditional Chinese medicine group increased significantly after the experiment（P<0.05）;Compared with the model group,alt,AST and TBi L in the traditional Chinese medicine group were significantly lower（P<0.05）.（6）The expression levels of serum IL-17,IL-17A and IL-23 in each group:compared with the Normal group,the levels of IL-17,IL-17A and IL-23 in the model group and traditional Chinese medicine group increased significantly after the experiment（P<0.05）;Compared with the model group,IL-17,IL-17A and IL-23 were significantly lower（P<0.05）.Conclusion:（1）Jiedu Huayu Granule can improve the mental condition,hair color gloss and defecation of ACLF rats,and increase the feeding of ACLF rats;（2）In ACLF rats,rat serum expression levels of IL-17,IL-17A and IL-23inflammatory cells were high,and hepatic inflammatory cells infiltrated significantly,and the liver was in a state of immune inflammation activation;（3）Detoxification stasis granules can reduce the expression of IL-17,IL-related inflammatory factors,IL-17A and I L-23,reduce liver inflammatory damage,improve ALT,AST and TBi L in ACLF rats,and improve the survival rate of ACLF rats,which may be one of the mechanisms by which detoxification stasis granules antagonize ACLF in rats.