| ObjectiveHepatitis B virus (HBV) is an infectious disease caused by hepatitis B virus infection, China is a high prevalence area, about300000people died due to liver disease each year, most of which are related with HBV infection, and the disease of10%-20%can be turned into liver cirrhosis or liver cancer, is a serious threat to our life and health. In chronic hepatitis patients, due to autoimmune disorders, antibodies produced by the body are not enough to clear the body of the hepatitis B virus, resulting in a large number of virus replication, continue to cause liver cell damage, eventually cirrhosis or liver cancer. Method for finding the exact effective and simple treatment of the disease more and more attention. According to the Qing Dynasty famous doctor Huang Yuanyu "circular flow of Qi, soil and pivot Sasang" medicine "see liver disease, liver Chuan spleen" theory, the "Treatise on the" side of Sini Decoction with hill dogwood and regulating the body’s immune based Modified Sini Decoction. The original Sini Decoction mainly treating deficiency of Yang Yin Han Sheng little cold syndrome, has the functions of Yang deficiency. Modern pharmacological research show that:Sini Decoction has shock resistance, strong heart, improve microcirculation, blood lipid and anti inflammatory, immune regulation and other pharmacological effects on the pathological state of the body. Cornus officinalis have been shown to have antioxidant, immunomodulatory, anti-inflammatory and other aspects. We observed the effect of Modified Sini Decoction in the treatment of chronic hepatitis B by clinical. Modern research thinks, hepatitis B is a kind of immune related diseases caused by the hepatitis B virus, tissue injury after HBV replication is not the direct role in the liver cell of the result of infection, but a series of host immune response caused by immune damage caused by pathological immune response in liver cells. Liver injury model and clinical hepatitis concanavalin copy form performance is very similar, as many commonly used models of viral hepatitis in the modern study of. Based on affirming the clinical curative effect on acute immune liver, by copying con damage model, to observe the protective effect of Modified Sini Decoction on immunological liver injury using flow cytometry, ELISA and other methods, and to explore its protective mechanism.MethodsClinical study:32cases of patients with chronic hepatitis B were observed by Modified Sini Decoction, traditional Chinese medicine treatment, daily1agent, the control group was treated with lamivudine treatment, daily100mg,3months to1course of treatment, a total of2courses of treatment, then analyze the changes before and after treatment, symptoms and signs, liver function and indexes of hepatic fibrosis.Experimental study:Female NIH mice were randomly divided into5groups: normal control group, model control group, positive drug group, Modified Sini Decoction Modified Sini Decoction in high dose group, low dose group, acute immune liver injury model by tail vein injection of Con A.12h after the death of animal liver and serum of mice were detected the liver index, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and liver tissue superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, and to observe the pathological morphology. Determination of blood CD4+, CD8+T lymphocyte subsets by FACS Cali bur flow cytometry, and the ELISA method for the determination of serum glutamic oxaloacetic transaminase (AST), alanine aminotransferase (ALT) activity and cytokines in mice tumor necrosis factor (TNF-a), mouse interferon R (IFN-r) and interleukin-10. All the data are mean+standard deviation said, statistical analysis was performed by SPSS17.0software, the measurement data between two groups were compared using t test, compared with single factor analysis of variance, between the two two groups were compared with LSD test statistics, all the data in each group were test of normality and homogeneity of variance test, take a=0.05is a significant test level. ResultsClinical study:two cases had no significant difference in age, gender and disease distribution. After treatment, the treatment group in the symptoms and signs were improved markedly, with statistical significance compared with the control group; but in the detection of liver function and hepatic fibrosis index, the two groups have no significant difference. Experimental study:1、 liver morphological changes.Macroscopic observation:normal liver morphology was normal, smooth, ruddy color. Model group liver volume increased, membrane swelling, blunt edge, surface punctate and patchy necrosis and hemorrhage, treatment group was close to normal. Microscopy:normal liver tissue of the group structure is complete, clear, liver cell degeneration, no necrosis, no inflammatory cell infiltration. Fuzzy damage model group, hepatic lobules, the most visible liver cells appeared punctate, patchy or diffuse necrosis, necrosis region has a large number of lymphocytes and mononuclear cells infiltration, the majority of intracellular phagocytosis of cellular debris and lipofuscin Kupffer cell hyperplasia; in addition, the majority of liver cell cytoplasmic swelling, osteoporosis, some are ballooning degeneration, and there were many round in eosinophil apoptosis eosin liver cells. Use structure of hepatic lobule were close to normal, reduce liver cell necrosis and inflammatory cell infiltration.2、 Effect of Modified Sini Decoction on immunological liver injury in mice, the levels of AST ALTResults liver function of mice showed, model mice of control group ALT, AST levels were significantly higher than that of control group (all P<0.05), compared with the normal group had statistical significance (P<0.01), showed that the experimental modeling success; compared with the model group, bifendate group and Modified Sini Decoction group four different levels reduced transaminase level (P<0.05), showed that Modified Sini Decoction group four can reduce the immunological liver injury in mice ALT and AST activity.3、 Effect of Modified Sini Decoction on mice liver homogenate SOD and MDAUsing Con A model, MDA levels in mice were significantly higher than that of control group, SOD activity was significantly lower than that in control group (P<0.01). After treatment, compared with model group, Modified Sini group Decoction SOD levels increased in different degrees (P<0.01), the level of MDA was significantly decreased (P<0.05).4、 Effect of Modified Sini Decoction on IFN-r, TNF-a and IL-10secretionThe results show that:the model control group IFN-r, TNF-a were significantly higher than that of control group (P<0.01); western medicine treatment group and Modified Sini group Decoction after treatment, compared with model group, IFN-r, TNF-a secretion decreased significantly (P<0.01); the content of IFN-r, TNF-a between treatment groups was not statistically significant (P>0.05). The content of serum IL-10and the model control group decreased significantly than that of control group (P<0.01); western medicine treatment group and model control group increased IL-10activity (P<0.01), but still lower than the control group; Modified Sini Decoction intervention, the content of IL-10was also improved, compared with the model group differences (P<0.05).5、 Effect of Modified Sini Decoction on peripheral blood CD3, CD4, CD8The experimental results show that the model group mice whole blood CD4+, CD8+ratio compared to the normal control group decreased significantly, there was significant difference compared with the normal group (P<0.05); compared with the model group, Modified Sini Decoction each dose group can cause mouse whole blood CD4+, CD8+ratio was significantly increased (P<0.05), Modified Sini Decoction CD4+, CD8+the ratio of blood mice have increased markedly lower in immunological liver injury in the higher ratio, namely peripheral blood T lymphocyte subsets, reduce its to liver infiltration, thereby reducing its cytotoxic effect on liver cell injury.ConclusionClinical research:Modified Sini Decoction in the treatment of chronic hepatitis B, have a better effect, especially for improving the quality of life of patients, in the improvement of liver function and prevent liver fibrosis also has curative effect, without obvious side effect. Experimental study:1、 Mice via tail vein injection of ConA12h, ALT, AST levels were significantly elevated, the serological indexes changes consistent with the reported literature, that liver injury rats.2、 Modified Sini Decoction can significantly decrease the serum transaminase mice model ALT, AST activity, that has protective effects on liver immune Modified Sini Decoction for Con A damage. And can obviously reduce the lobules liver injury mouse immunological liver damage, reduce the infiltration of inflammatory cells in the liver tissue, reduce the formation of necrosis and apoptosis of liver cell degeneration,, to protect the liver tissue objective.3、 Modified Sini Decoction could significantly increase the activity of SOD of liver injury model of mouse liver tissue, while reducing the content of MDA, show that it has certain antioxidant on immunological liver injury in mice, reduce the production of free radicals, reducing liver peroxidation. The mechanism may be directly scavenging free radicals, free radical chain reaction chain blocked or terminated, so as to prevent or inhibit the reaction of oxygen free radical and lipid peroxidation, generate the final inhibition of lipid peroxidation product MDA. Therefore, Modified Sini Decoction may be through the cell membrane stability, resisting lipid peroxidation and blocking apoptosis reached against liver injury, and its mechanism of action remains to be further studied body.4、 Modified Sini Decoction can significantly decrease the levels of serum IFN-r, TNF-a model in mice, increase the level of IL-10, so we speculated that Modified Sini Decoction by downregulating the excessive proinflammatory cytokines and anti-inflammatory cytokines release to protect the immune liver injury.5、 Modified Sini Decoction upregulated significantly decreased in peripheral blood of the mouse model of CD4+, CD8+ratio, that proportion of T lymphocyte subsets in peripheral blood of Modified Sini Decoction can improve the model mice, reduce the liver infiltration, thereby reducing the cell toxicity to liver cells, so we speculated that the immune response level effect of Modified Sini Decoction to protect the liver injury and regulation of T cell subsets in mutual equilibrium and in the process of liver injury in mice. |
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