| Hepatitis B is one of the most common infectious diseases in the world. Hepatitis B virus (HBV) is a major pathogen of acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma. It has been estimated that 350 million people worldwide are chronic hepatitis B virus carriers. The global prevalence of chronic HBV infection varies widely. Asia is the area of the high prevalence of chronic HBV infection. In the areas of high endemicity, perinatal transmission is the main route of transmission. One-quarter to one-third people infected chronically with HBV is expected to develop progressive liver disease (including cirrhosis and hepatocellular carcinoma).Hepatitis B is an important public health issue. There have been many studies on the immunopathgenesis of Hepatitis B. It is well known that the host response to the virus must have a critical role in the pathogenesis of the associated diseases. The precise pathogenetic mechanisms responsible for the various forms of acute and chronic liver diseases are only partly defined. HBV middle protein has stronger immunogenicity. It can induce strong humoral and cell-mediated immune responses. It is unclear whether humoral and cell-mediated immune response related with the middle protein can cause liver lesion. The pathogenesis of hepatitis B and the liver lesion resulted from humoral and cell-mediated immune response in hepatitis B transgenic micewas investigated. Hepatitis B virus core protein, as well as HBV middle protein, can induce stronger humoral and cell-mediated immune responses. It is unclear whether humoral and cell-mediated immune response related with the core protein can cause liver lesion. The function of hepatitis B virus core protein and its interaction with other hepatitis B proteins are unclear. Transgenic model is a useful system to identify the function of core protein and may be an ideal experimental model to investigate the function of core protein. It could provide new insights into core protein. This experiment includes two parts.Part one: Immunopathogenesis of liver lesion resulted from immune response about HBV middle protein in HBV transgenic miceHBV transgenic mice Balb/c-TgN (preS2.S/ayw) were mated with same linage mouse. Mice were screened by PCR and immunohistochemical analysis. To study the pathogenesis of hepatitis B and the liver lesion resulted from humoral and cell-mediated immune response in hepatitis B transgenic mice Balb/c-TgN (preS2.S/ayw) , anti-sera and primed spleen cells were collected from the normal Balb/c mice injected on a single occasion with 100ug recombinant DNA (pcDNA3-S2.S) encoding HBV middle envelope protein . DNA was injected directly into regenerating tibials anterior muscles . An Hepatitis B transgenic mouse lineage Balb/c-TgN (preS2.S/ayw) model system was used to analysis the immunopathogesis of HBV-induced liver disease. Anti-sera and primed spleen cells were collected. And anti-sera> primed spleen cells(recipient mice with 5Gy irradiation), anti-sera+primed spleen cells(recipient mice with 5Gy irradiation), primed spleen cells(recipient mice without 5Gy irradiation), normal spleen cells, anti-HBs antibody and anti-preS2 antibody were passively transferred into transgenic mice (harbouring HBV preS2 and S genes) and their nontransgenic littermates. Blood was collected from anesthetized mice by retrobulbar puncture using heparinized glass pipettes at various intervals (0, 2 or 4, 7, 14 or21 d)after immunization to measure the level of HBsAg, anti-HBs antibody, preS2antigen , anti-preS2 antibody, ALT, AST, Cr and Urea. At meanwhile, the tissues of mice were fixed in formalin. Paraffin embedded tissues were sectioned and stained with hematoxylin/eosin. The expression of hepatitis B surface antigen was assessed by immunohistochemical analysis.The immunization in mice was induced efficiently. After passive transfer of anti-sera, the pathological changes in the liver of the transgenic mice resembled what were observed in human acute hepatitis B. The pathological change of liver was chara...
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