Study On Clinical Observation Mechanism Of Treating Hepatitis B Liver Fibrosis By Wenjing Decoction Based On NF-κB/NLRP3 Inflammasome Pathway

Objective: By observing the clinical effect of Jiawei Wenjing Decoction on patients with chronic hepatitis B liver fibrosis,the rat model of liver fibrosis was established,and the mechanism of Jiawei Wenjing decoction reducing inflammatory injury and degree of liver fibrosis through NF-κB/NLRP3 inflammasome pathway was discussed,providing more scientific theoretical basis for the treatment of chronic liver disease by traditional Chinese medicine.Methods:1.Clinical study: 60 patients with posthepatitis B liver fibrosis were randomly divided into control group and observation group,with 30 cases in each group.The control group was treated with Entecavir capsule,and the observation group was treated with supplemented warm Jing decoction on the basis of the control group.The course of treatment of the subjects was 6months.After treatment,the subjects were evaluated for safety,and the changes of TCM syndrome score,clinical effective rate,liver function,liver fibronectin,serum interleukin-6(IL-6)and liver hardness(LSM)were compared between the two groups.Animal experimental study: 34 SPF SD rats were fed with normal diet under normal conditions for 1 week,and 6 rats were randomly divided into blank group,and the remaining 28 rats were injected intraperitoneally with 40%carbon tetrachloride olive oil solution(2:3)at the rate of 0.3ml/100 g body weight,twice a week,for consecutive 8 weeks.At the end of the 8th week,3experimental rats were randomly selected to build the model,and then the remaining experimental rats were randomly divided into model group,Jiawei Wenjing decoction high-dose,medium-dose and low-dose groups,with 6experimental rats in each experimental group.After successful modeling,Jiawei Wenjing Decoction low-dose,medium-dose and high-dose groups were respectively given a certain concentration of traditional Chinese medicine intragastric treatment,blank group and model group were given equal volume of distilled water intragastric treatment,once a day for 4 weeks,and then the pathological changes of the experimental rats’ liver were observed.The contents of ALT,AST,ALB and TBIL in serum of experimental rats were determined and analyzed by automatic biochemical analyzer,and the contents of TNF-α,IL-6,IL-β and IL-18 in serum of experimental rats were detected by ELISA.The protein expressions of NF-κB and NLRP3 in rat liver were detected by Westernblot.Results:1.Clinical research: After treatment,TCM clinical syndrome score,total clinical efficacy,liver function,liver fiber,IL-6 and LSM in 2 groups were significantly improved compared with before treatment(P<0.01 or P<0.05),and the above indexes in observation group were better than control group(P<0.01 or P<0.05).During clinical treatment,No adverse events were observed in both groups.Animal experimental studies:(1)HE staining showed that a large number of liver cells in the model group were degenerated and necrotic,the normal structure of hepatic lobules was destroyed,and a large number of inflammatory cells were infiltrated.(2)Compared with model group,the levels of ALT,AST,TBIL,TNF-α,IL-6,IL-1β and IL-18 in the high-dose,medium-dose and low-dose groups of Supplemented Wenjingtang were decreased,and the expressions of NF-κB and NLRP3 were decreased.The effect of Jiawei Wenjing Decoction(high-dose and medium-dose)group was the most obvious(P < 0.01).The serum ALB level in Jiawei Wenjing decoction low-dose group was higher than that in model group,but there was no statistical significance.Conclusion(s):1.Clinical study: Entecavir combined with Wenjing Decoction can significantly improve the clinical symptoms and TCM syndrome scores of hepatitis B fibrosis patients with Yang deficiency and blood stasis,improve liver function,reduce inflammatory damage and fibrosis,and it is safe and reliable.The longer the drug duration,the more obvious the effect.2.Experimental study: Wenjing Decoction have protective effects on CCl4-induced rat hepatic fibrosis model,the mechanism of which may be related to down-regulating the expression of related protein of NF-κB/NLRP3 signaling pathway,reducing the level of related cytokines,and inhibiting the activation and proliferation of HSC.