Fuzheng Qudu Decoction Interferes With The Mechanism Of Immune Tolerance In Mice Bearing Chronic Hepatitis B Virus

Objective:The Chronic Hepatitis B virus carriers represent a particular group of patients with Hepatitis B virus infection.Although the aminopherase(transaminase?)level is in most cases within normal range,and typically without liver histological abnormalities,such patients are characterized by HBeAg and HBsAg positive,and high replication of HBV DNA,which often cause insidious development from Hepatitis B to liver cirrhosis or live cancer.Immunological tolerance is the core mechanism of chronic hepatitis B virus infection.In view of the compatibility of immune tolerance in chronic hepatitis B virus carrier and the "vital qi weakness and incubation of toxic" theory,this experiment proposes an early and continuous intervention of mice carrying chronic hepatitis B virus with the Fuzheng Qudu formula,which has the efficacy of "maintenance of vital qi and detoxification".Taking related cytokines as the point of observation,this experiment records changes in HBsAg,HBeAg,transaminase and the liver tissues of the mice carrying chronic hepatitis B.By doing so the experiment also investigates the mechanism of the Fuzheng Qudu fromula in regulating the immune function of chronic hepatitis B virus in mice.Method:Randomly divide male HBV transgenic mice aged 8-12 weeks into model group,western medicine group and Chinese medicine group of equal size,with a fourth blank group.All four groups are raised normally.In the first week of intragastric administration,the Chinese medicine group was given the Fuzheng Qudu formula.The western medicine group was given comparator drugs.After 24 weeks,the animals were killed and samples were obtained.We use automatic biochemical analyzer to test level of ALT,AST in the serum of mice;use the CLIA to measure HBsAg,HBeAg level;use the ELISA method to measure IFN-γ TNF-α、IL-10;take mice liver tissue and use HE staining to observe pathological changes.Result:1 General situation:Mice in the model group and the western medicine group had dull skin and fur,and were less active and had less food intake.Mice in the Chinese medicine group and the blank group had good gloss,liveliness,and normal food intake.2 Transaminase:levels of AST and ALT in the model group were higher than that in the blank group(P<0.05);levels of AST and ALT in the Chinese medicine and Western medicine group were lower than that of the model group(P<0.05).3 HBsAg and HBeAg:3.1 HBsAg:The rates of HBsAg positive in the blank group,model group,western medicine group and Chinese medicine group were 0%,100%,100%and 100%,respectively.3.2 HBeAg:The rates of HBeAg positive in the blank group,model group,western medicine group and Chinese medicine group were 0%,100%,71.4%and 57.1%,respectively.The Chinese medicine group had a serological conversion rate of 42.9%,the Western medicine group had a serological conversion rate of 28.6%(Negative<1,Postive≥1).4 Expression of cytokine in mouse hepatocytes:IFN-y:the model,Chinese and Western medicine groups had lower IFN-y value than blank group(P<0.05);the Chinese and Western Medicine groups had higher IFN-γ value than the model group(P<0.05).TNF-α:the model,Chinese and Western medicine groups had higher TNF-a value than the blank group(P<0.05).IL-10;the model,Chinese and Western medicine groups had higher IL-10 value than the blank group(P<0.05);The Chinese medicine group had lower IL-10 value than the Western medicine and model groups(P<0.05).5 Pathological changes in liver tissue:Compared with the blank group,the liver lobule structure in the model group was in disorder.The fibrous tissue and infiltration of inflammatory cells were seen in the liver tissue.Compared with the blank group and the model group,only a small amount of fibrous tissue was formed around the portal area in the western medicine group.The liver samples of the Chinese medicine group were similar to those of the blank group,and no pathological changes were observed.Conclusion:1 The Fuzheng Qudu formula can alleviate the inflammatory damage in mice with chronic hepatitis B virus and delays the process of liver fibrosis.2 The Fuzheng Qudu formula can inhibit the expression of HBeAg in chronic hepatitis B virus carrying mice,thus inhibiting the replication of HBV.3 Te Fuzheng Qudu formula can up regulate the expression of IFN-γ and down regulate the expression of IL-10,thereby reinvigorating the dormant cellular immunity,which is helpful for the body to clear the virus.4 The Fuzheng Qudu formula with its efficacy of "maintenance of vital qi and detoxification" can improve the prognosis of Chronic hepatitis B virus carrying mice.Possible mechanism can be the regulation of cytokines expression and inhibition of the replication of the virus and thus the delay of formation of liver fibrosis.