Study On The Mechanism Of Liver Cirrhosis Treatment Based On Nrf2/ARE Signaling Pathway

Objective: To observe the clinical efficacy of Chaihu Danggui powder combined with entecavir in the treatment of patients with hepatitis B cirrhosis in compensated stage.Furthermore,a rat model of liver cirrhosis was established,and it was preliminarily explained that the treatment of liver cirrhosis by Chaihu Danggui Powder may be related to the regulation of Nrf2/ARE signaling pathway to exert an anti-oxidative stress mechanism.This enriches the theoretical connotation of traditional Chinese medicine in the treatment of liver cirrhosis and provides a scientific basis for the clinical application of traditional Chinese medicine in the treatment of early liver cirrhosis.Methods:(1)Clinical observation: 64 patients with liver stagnation and spleen deficiency with stasis syndrome were selected and randomly divided into treatment group(n=32)and control group(n=32).Among them,the control group was treated with entecavir(ETV),and the treatment group was treated with Chaihu Danggui powder on the basis of the control group.After 3months and 6 months of treatment,the TCM syndrome scores,liver and liver syndrome scores of the two groups before and after treatment were compared.Function [alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB),serum total bilirubin(TBIL)],liver fiber four items[hyaluronic acid(HA),procollagen type(PC-III),collagen type IV(IV-C),laminin(LN)],serum superoxide dismutase(SOD),liver stiffness value(KPA)value changes.(2)Animal experiment: 28 SPF-grade SD healthy rats were adaptively fed for 7 days,and 8 healthy rats were randomly divided into blank group,and the remaining rats were divided into carbon tetrachloride and olive oil solution(2:3)Liver cirrhosis was modeled by subcutaneous intraperitoneal injection,and the modelling time was 8 weeks.In the 8th week,4 rats were randomly selected to be sacrificed,and their liver histopathological sections were taken to prove the successful modeling of liver cirrhosis.After successful modeling,they were divided into model group and traditional Chinese medicine group,8 animals in each group,blank group,model group and distilled water gavage,and traditional Chinese medicine group gavage with Chaihu Danggui powder suspension.Bupleurum angelica powder suspension and drinking water were administered by gavage once a day,starting from the beginning of the ninth week,for four consecutive weeks,and ending at the end of the 12 th week.After the intervention,the general condition of the rats was observed and the serum ALT,AST,ALB,TBIL,SOD,GSH and MDA of each rat were detected;HE staining was used to observe the pathological changes of liver tissue and Western blot was used to detect the Nrf2 and HO-1 of liver tissue.protein expression.Results:(1)Clinical study: After treatment,the clinical comprehensive curative effect and TCM syndrome scores of the two groups were improved compared with those before treatment(P<0.05),and the overall curative effect and TCM syndrome scores of the treatment group were better than those of the control group(P<0.05).The levels of ALT,AST,TBIL,ALB,liver fiber,and liver stiffness in the treatment group were lower than those in the control group(P<0.05).The SOD level in the treatment group was higher than that in the control group(P<0.05).During the clinical treatment period,there were no obvious adverse reactions in the two groups of patients.(2)Animal experiment: 1.General condition of rats: After intervention treatment,the mental state,diet,drinking water,activity level and coat color of the rats in the Chaihu Danggui powder group were improved to varying degrees compared with the model group.2.HE chromosome in liver tissue: the arrangement of liver cells is disordered,degeneration and necrosis can be seen,and pseudolobules are formed,indicating that the modeling is successful.The fibrosis,degeneration and necrosis of the rat liver were improved to varying degrees after the intervention of Chaihu Danggui Powder.3.The numerical changes of peripheral blood ALT,AST,ALB,TBIL,SOD,GSH and MDA in the three groups of rats: compared with the blank group,the levels of ALT,AST,ALB,TBIL and MDA in the model group increased(P<0.05),The levels of SOD and GSH were decreased(P<0.05);compared with the model group,the levels of ALT,AST,ALB,TBIL and MDA in the Chaihu Danggui powder group were recovered,and the levels of SOD and GSH were increased,and the difference was statistically significant(P<0.05).0.05).4.The expression of Nrf2 and HO-1 protein in rat liver tissue: Compared with the model group,Nrf2 and HO-1 in the Chaihu Danggui powder group increased to different degrees,and the difference was statistically significant(P<0.05).Conclusion: Clinical studies show that entecavir combined with Chaihu Danggui powder can effectively reduce TCM syndrome scores in patients with hepatitis B due to liver stagnation and spleen deficiency and stasis,improve the total clinical efficacy,improve oxidative stress,protect liver cells,and reduce liver fibrosis.,and safe and reliable,the longer the medication time,the more obvious the curative effect.In terms of animal experiments,in the liver cirrhosis model rats successfully induced by CCL4,hepatocytes were destroyed and pseudolobules were formed.Bupleurum Danggui powder not only restored the function of liver cells,but also reduced the formation of liver tissue fibrosis,which may be related to the activation of Nrf2/ The ARE signaling pathway and the activities of its downstream antioxidant enzymes such as SOD,GSH,HO-1,etc.reduce oxidative stress and exert an antioxidant mechanism.