| 【Backgroud】Fifty years ago, Waldenstron and Kunkel first described a type of chronic hepatitis mainly in white young women, characterized by anti-nuclear antibody (ANA) appeared in serum. Since then, the relevant reports have been increasing. Until the 1992 International Conference on autoimmune hepatitis holding on, these hepatitis reports would be formally named the autoimmune hepatitis (autoimmune hepatitis, AIH). AIH is closely related with the autoimmune response of a substantial damage to the liver disease, and which is characterized by high C hypergammaglobulinemia, serum autoantibodies, chronic inflammation and fibrosis of the liver histological changes. The etiology and pathogenesis so far not been fully elucidated, the pathogenesis may involve genetic susceptibility factor, liver cell injury, immune regulatory network and cross-reaction (molecular modeling) and so on. Explore the etiology and pathogenesis of the disease, not only conducive to the early diagnosis of the disease, but also to promote the emergence of new treatments and ultimately achieve the purpose of improving the quality of life of patients.Now an animal model of AIH has been widely recognized at home and abroad , that is to use the same germ-line liver antigen of the animals susceptible C57BL/6 mice emulsified in complete Freund's adjuvant injections to induce experimental autoimmune hepatitis (EAH) after twice intraperitoneal. The histological changes in the liver of this model is very similar to liver histological features of human with autoimmune hepatitis, that both have a large number of inflammatory cells in particular infiltrating lymphocytes, and with varying degrees of liver necrosis and serum transaminase increased. And the autoantibodies can be detected by immunofluorescence.Fibroleukin (fibroleukin) or fgl2 prothrombinase (the fgl2) is a member of the fibrous protein family, which can be divided into Fgl2 Cross model and Fgl2 secreted. The former can catalyze prothrombin into thrombin and activate the clotting process. The latter mainly secreted by T cells, which is play a role in the Inhibition of immunity in the T cell proliferation and dendritic cells (DC) mutations. In the mouse model of fulminant hepatitis, mouse fgl2 prothrombinase (mfgl2) selectively highly expressed in liver disease tissues whose gene expression level is closely related to liver fibrin deposition and extensive necrosis of liver cells. In liver tissues of the Severe Hepatitis B patients we can also found a high degree expression of fgl2 prothrombinase in macrophages and endothelial cells. In a variety of autoimmune-related diseases such as graft with the germ line rejection, systemic lupus erythematosus and so on, the expression of fgl2 were also observed . As for fgl2 is whether to expression and play role and function in autoimmune liver diseases rarely reported. Therefore, this study specially collected peripheral blood and liver puncture specimens of the clinical patients, and established the mouse model of autoimmune hepatitis, in order to explore the relationship with fgl2 and autoimmune hepatitis, and to further study the pathogenesis of autoimmune diseases function.【Objective】1. To investigate the hfgl2 expression in puncture specimen and peripheral blood mononuclear cells(PBMCs) of clinical patients with AIH.2. To establish experimental autoimmune hepatitis model for studing the mfgl2 expression in liver, spleen and PBMCs. 【Methods】1. Collected and selected some samples of AIH from outpatients and hospitalized patients in Tongji hospital between 2008 and 2009 to acquire asolated PBMCs for detection of hfgl2 expression by immunocytochemistry and Real-time PCR reaction, and puncture specimen for detection of hfgl2 expression by immunohistochemistry, pathological changes and collagen fiber deposition with liver tissue HE staining and Masson staining.2. Set up and observe the mice model of experimental autoimmune hepatitis(EAH): the syngeneic S-100 hepatic antigen emulsified in complete Freud's adjuvant(CFA) was injected intraperitoneally at day 0 and day 7 with susceptible C57BL / 6 mice, and compared with normal group untreated. At day14 asolated the PBMCs of mice, made cell smears and paraffin section of liver and spleen tissues to detect expression of mfgl2 by immunohistochemistry and detected liver histopathology and serum chemistry changes.【Results】1. Compared with healthy, the expression of hfgl2 in AIH liver puncture specimens increased significantly, and it mainly expressed in lymphocytes cytoplasm and liver cell nuclei of point necrosis areas and inflammatory infiltration areas. The expression of hfgl2 mRNA in PBMC of AIH patients was higher than healthy controls.2. In the mice model of experimental autoimmune hepatitis, the cytoplasm of lymphocytes in the liver and spleen and PBMCs highly expressed mfgl2, while the normal group, no obvious mfgl2 expression.【Conclusion】Fgl2 highly expressed in lymphocytes of liver and PBMCs both in AIH patients and experimental autoimmune hepatitis mice compared with the normal control, it indicates that fgl2,especialy secreted fgl2 is involved in the lymphocyte-related immune function. Fgl2 plays an important role in the development of autoimmune hepatitis... |
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