Research On The Effects And Mechanisms Of Qizhu Decoction Treating CHB

Background:Chronic hepatitis B, hepatitis B virus (HBV) infection, liver damage caused by the humoral and cellular immune systemic disease. The wide range of the epidemic spread of the complexity of ways, the high incidence of the dangers of large, ranking the first of a variety of infectious diseases, and infectious diseases of serious harm to human life and health. Chronic hepatitis B worldwide distribution, more than20million people are infected worldwide, about350million people with chronic HBV infection. About50%-75%of the chronic hepatitis B patients with active viral replication and liver inflammation change, of which10%to20%may develop cirrhosis, and1%to5%may develop into liver cancer. Chronic hepatitis B is a human disease, the cause of death in the WHO announced nine diseases. Modern medical treatment, including the liver, reducing enzyme, antiviral, immunomodulatory, and effective anti-viral therapy cure for chronic viral hepatitis. The goal is to clear or sustained suppression of HBV to prevent or reduce liver inflammation, necrosis. A large number of clinical studies confirmed the ideal antiviral drugs interferon and nucleoside analogues. But interferon adapt narrow obvious side effects, long-term effect is not satisfactory, the price is expensive. Nucleoside analogues are prone to virus mutation, its clinical application is limited. A large number of clinical and experimental studies confirmed that the traditional Chinese medicine to protect liver cells, immune regulation, anti-fibrotic, and then by the combined effects of inhibition of viruses and other shows superiority. Not uniform, but the understanding of the Traditional Chinese Medicine Research surviving many problems, such as the so far Chinese medicine for chronic hepatitis B etiology and pathogenesis, syndrome diagnosis liver histopathological grading and commonly used in the international stage, typing clinical manifestations of chronic hepatitis B diagnostic criteria are incompatible, chronic hepatitis B is difficult to accurately reflect the severity of the clinical treatment of the lack of effective, science, systems can not meet the chronic hepatitis B in Chinese medicine clinical requirements.Objective:explore stilbene beads side through experimental research, the treatment of chronic hepatitis B mechanism, clear the stilbene beads prescription drug composition characteristics, looking for clinical lay the foundation for effective medicine in the treatment of this disease.Qizhu decoction side by Phyllanthus, Polygonum cuspidatum, Radix, TPG, diffusa, soil Fuling Qiwei drug composition, the maximum in order to ensure the efficacy of active ingredients, chosen for this study heating reflux extraction by RP-HPLC analysis of the chemical composition of the compound, and choose one of four different concentrations of ethanol extraction and analysis of the changes in the chemical composition of samples of different solvent extraction. Establishment of animal models of liver fibrosis based on traditional Chinese medicine, the middle dose group were16.20g/kg,9.72g/kg (Qi Zhu Fang Sheng the medicine content/rat body weight) orally, once a day, for the first time modeling the administration began the next day, for eight consecutive weeks until the animals were killed the day before; colchicine group (ground, made of an aqueous solution of colchicine tablets per1mL of water containing0.1mg colchicine)5.0mL/kg (colchicine alkali content/rat body weight) orally, once daily, the model for the first time the next day, the administration began eight consecutive weeks until the animals were killed the day before; model group, the same as the the stilbene beads Fangda dose group was given volume of physiological saline gavage, liver tissue TNF-a, IL-4, IL-8, IL-10, TIMP-1, MMP-1, MMP-2, MMP-13expression levels, serum TIMP-1, MMP-1, MMP-2, MMP-13expression.Results:different solvent extraction stilbene beads side (70%alcohol into the sample to80μL, the rest are10μL) sample obtained a number of peaks, mentioned by50%of water,70%,95%compound extracted basic25min before does not have a peak, during the experiment, by increasing the injection volume comparison,70%ethanolic the stilbene beads side peaks up to the size and shape of the peak shape better. Liver fibrosis model in animal models of rats liver tissue TNF-a, IL-4, IL-8expression relative blank group significantly increased IL-10expression significantly reduced liver tissue TNF-a, IL-4, the expression of IL-8was significantly (P<0.01) reduction in the expression of IL-10’s significantly with increased (P<0.01); stilbene beads side high dose group of TNF-a, of IL-4, of IL-8’s expression lower than the middle dose group IL-10expression is higher than the middle dose group; the stilbene beads to water extraction group, IL-4, IL-8, TNF-a expression is lower than the same dose of ethanol extract group, IL-10expression is higher than the same dose of ethanol extract group (P<0.01). Expression of IL-4compared to colchicine group, stilbene the beads side treatment group were higher than the colchicine group and there is a significant difference (P<0.01); stilbene beads to treatment group of IL-8expression was significantly higher than in autumn Narcissus alkali group (P<0.01); the stilbene beads to treatment group the expression of IL-10were lower than the colchicine group and a significant difference (P<0.01); the stilbene beads to treatment group were higher than the expression of TNF-a colchicine alkali group (P<0.01). Model group, TIMP-1, MMP-2expression is relatively higher than the normal group, MMP-1, MMP-13expression is relatively lower than the normal group, the two groups differ significant differences (P<0.01). All treatment groups TIMP-1, MMP-2expression is lower than the model group, MMP-1, MMP-13expression is higher than the model group, there were significant differences (P<0.01). Stilbene the beads side high dose group of TIMP-1, MMP-2expression is lower than the middle dose group, MMP-1, MMP-13expression is higher than the middle dose group, significant dose-dependent manner (P<0.01). The stilbene beads to water extraction group, TIMP-1, MMP-2expression is higher than the same dose of ethanol extract group (P<0.01), MMP-1, MMP-13expression were lower than the same dose of ethanol extract group (P<0.01). TIMP-1expression stilbene beads side4treatment groups were higher than the colchicine group compared with the colchicine group, and there is a significant difference (P<0.01); expression of MMP-1in the high-dose group was significantly higher than in autumn Narcissus alkali group (P <0.01), the expression of the middle dose group below the colchicine group in alcohol extract dose group difference (P<0.05) were significantly different (P<0.01), water extraction in the dose group; expression of MMP-2treatment groups were lower than the colchicine group, compound high-dose group and the alcohol extract group, middle dose group, a significant difference (P<0.01), no significant water extraction in the dose group (P>0.05); the stilbene beads Fangda dose group MMP-13expression above the colchicine group (P<0.01), the middle dose group was lower than the colchicine group (P<0.01). Model group, serum of TIMP-1, MMP-2expression is relatively higher than the normal group, MMP-1, MMP-13expression is relatively lower than the normal group, the two groups differ significant differences (P<0.01). All treatment groups serum TIMP-1, MMP-2expression is lower than the model group, MMP-1, MMP-13expression is higher than the model group, there were significant differences (P<0.01). Stilbene the beads side high dose of serum TIMP-1, MMP-2expression is lower than the middle dose group, MMP-1, MMP-13expression is higher than the middle dose group, significant dose-dependent manner (P<0.01). Stilbene beads to water extraction group dose serum TIMP-1expression extract the middle dose group (P<0.01) higher than the same dose of alcohol, the high-dose group was not statistically significant (P>0.05); MMP-1water extract group expression were lower than the same dose of alcohol extract group (P<0.01) higher than the same dose of alcohol extract group (P<0.01); aqueous extract group, the expression of MMP-2; MMP-13expression were lower than the same dose of ethanol extract group (P<0.01). TIMP-1expression compared with colchicine, stilbene beads side4treatment groups were higher than the colchicine group, large water extraction, the middle dose group and the alcohol extract middle dose group were significantly different (P<0.01) alcohol extract high-dose group was not statistically significant (P>0.05); MMP-1expression in the high-dose group than colchicine group (P<0.01), the middle dose group was lower than the colchicine group (P<0.01); expression of MMP-2treatment group were lower than the colchicine group, compound high-dose group and the alcohol extract group, middle dose group, a significant difference (P <0.01), the water was no mention in dose statistically significant (P>0.05); the stilbene beads Fangda dose group MMP-13expression is higher than the colchicine group (P<0.01), the middle dose group was lower than the colchicine group (P<0.01).Conclusion:Qizhu decoction party alcohol extract to treat chronic hepatitis B and liver fibrosis by regulating the liver and serum TNF-a, IL-4, IL-8, IL-10, TIMP-1, MMP-1, MMP-2, MMP-13.