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The Research Of The Mechanism Of Acetate Alisol B To Restrain Hepatitis B Virus

Posted on:2011-05-26Degree:MasterType:Thesis
Country:ChinaCandidate:C Z HuFull Text:PDF
GTID:2144360305963155Subject:Integrative basis
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Hepatitis is a kind of serious infectious virusis caused by Hepatitis B virus. According to the reports from WTO, over 2 billion people are HBV carriers, and more than 300 million are chronic infected. About half of the HBV infected people are in our country. The number of the HBsAg carriers is 9.3 million till 2008 in China and increase with 2 million every year. Compared with those non-HBV carriers, the HBV carries faced with much higher risk of liver cancer and cirrhosis. With the therapy of HBV vaccine and other anti-HBV medicines, which makes the HBV virus variating quickly, increases more and more chronic HBV infected patients. Scientists find out that the cccDNA of the HBV virus exits in the liver is the key to the chronic infection of HBV. So people put more energy in seeking for the medicine witch can erase viral cccDNA in liver, and make it possible to heal the HBV carriers completely.The HBV replication includes four classes:first, the virus exuviates adventitia and enters into the infected hepatocytes with phosphorylase, the virus draws off the capsid protein and turn to the structure of cccDNA. cccDNA is the HBV replication template, and it also can transcript to mRNA. Then the virus integrates pre-RNA with the instruction of mRNA, and envelops with capsid in extranuclear. The virus reverses transcripts to negative DNA chain with the pre-RNA as template, and synthesizes to positive DNA chain. At last the complete virus which has infectious ability is secreted to extranculear to maintain the numbers of cccDNA. So blocking off the every step of viral replication is the key to heal hepatitis B disease.In a great deal of researches, scientists find that the liver damage is caused by cell-mediated immunity but not the HBV virus itself. In the course of HBV infection, the monocyte-macrophage cells incepts and processes the viral antigen, then submits to the Th cell. With the IL-1 secreted from macrophage, the Th-cells are activated to multiplication and release IL-2. Then the sensitized Tc cells proliferate and turn into effect T cells. The effect T cells attack the hepatocytes affected by HBV virus, which lead to the liver damage. The scientists think the hepatocytes which can express target antigen and type 1 MHC antigen can be attacked by the Tc cells. And the apoptosis of cells and the viral infection are also the reasons of the damage-too.My experiment is based on the mechanism of the HBV infection and the relationship between the chronic hepatitis B and cccDNA to describe the anti-HBV effect of Acetate alisol B. Acetate alison B is isolate from Radix Astragliz. In traditional Chinese medicine, Radix Astragliz attributes to sweet, light, cold, owned by the kidney and bladder, used in diuresis.And the compounds of Radix Astragliz is very complicated. The Acetate alisol B attributes to triterpenoid compounds of classes. It has many activated functions, such as inducing tumor apoptosis, enhancing the sensitive of the cells to the anti-tumor medicine, inhibiting hypersensitivity and the synthesis of NO, restraining HBV virus. So Acetate alisol B is very potential in anti-HBV medicine research.We detect the viral DNA replication, and the presence of viral cccDNA in vivo and in vitro synchronously. In the assay, we found that different results showed in different cell models. On the HepG2.215 cell model, the TC50 of Acetate alisol B was 23.71mM, and the therapy index (TI) of HBsAg and HBeAg were 1.15,0.74 respectively, which showed that the Acetate Aliso B had not anti-HBV effect on HepG2.215 cells. But strangely, the data on primary duck hepatocyte cells showed that the Acetate Aliso B had a great anti-HBV effect on it. The TI of Acetate also B on restrain DHBV DNA was 4.08. The anti-HBV effect of Acetate alisol B is not apparent in HepG2.215 cells, but shows preliminary effect in vivo. So we surmise the Acetate alisol B has the effect to restrain HBV after metabolism in liver.
Keywords/Search Tags:Acetate Alisol B, 2.215 cell line, anti-HBV, HBV cccDNA
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