| [Objective]To observe the dynamically changing relationship between hepatic fibrosis and expression of cytokine interleukin-4,interferon-γ,in rats infected with Pagumogonimus skrjabini liver damage of different periods,To explore the function and significance of interleukin-4,interferon-γ,in liver fibrosis formation and regulation of rats infected with Pagumogonimus skrjabini,and thus know the role and significance of the Th1/Th2 in rats infected with Pagumogonimus skrjabini liver fibrosis formation and regulation.To further study the mechanisms of celluar immune response in liver fibrosis of rats infected with Pagumogonimus skrjabini.[Methods]36 rats were randomly divided into two groups:the control group and infection group.There were 6 rats in the control group,30 rats in the infection group.The animal model were set up by the way of peritoneal injection of Pagumogonimus skrjabini metacercaria to infect rats.Infection group were divided into 6 groups according to infection time:A group(infection for 1 week),B group (infection for 2 weeks),C group(infection for 4 week),D group(infection for 8 week),E group(infection for 12 week),F group(infection for 16 week).All rats were killed in corresponding tine points after being infected.then,there liver tissues were fixed,at last,they were made into paraffin sections,HE staining,VG staining,and observed the extent of liver necrosis and collagen distribution by light microscopy meanwhile,measured the dynamic chang of expression of interleukin-4,interferon-γ, in the formed process of liver fibrosis in rats infected with Pagumogonimus skrjabini by the use of immunohistochemical. [Results]In control group,the results of HE staining and VG staining showed liver cells were arranged regularly and the structure of hepatic lobules were integrated in liver tissue.Only there were trifle fibres in the vessel wall,no fiber connective tissue hyperplasia and inflammatory cell infiltration around the portal area.The results of immunohistochemical showed cytokines interleukin-4,interferon-γ,did not almost express in the liver.In infection group,there were hepatocellular edema in the integrated of the structure of hepatic lobules in A group,in B group,there were extensive fatty degeneration and a spot of balloon-like degeneration of liver cells in the structure of hepatic lobules,there were a large number of inflammatory cells infiltration and a small number of pumctiform necrosis in the centralvenous and protal area,no fiber fibrous connective tissue hyperplasia by VG staining.in C group,there were more significant balloon-like degeneration,necrosis and inflammatory cell infiltration in the integrated structure of hepatic lobules than B group,and appeared patchy necrosis,a litter of fiber fibrous connective tissue hyperplasia by VG staining.In D group,the obvious chang of pathology was acute purulent inflammation in liver.A mall obscess was formed in the liver tissue.In E group,the flaky fibrous tissue hyperplasia,the some blood essels and small bile duct hyperplasia appear in liver tissue,the structure of some hepatic lobules were damaged,reconstructed,fiber hyperplasia in part of doortude area.hyperplasia fiber were formed cord.To stretch into hepatic lobules,there were minority lymphocytes,neutrophil infiltration in hyperplasia fiber.In F group,a large of liver cells appeared necrosis,hyperplasia fiber were formed cord,the structure of hepatic lobules a were disorder,then appeared further bridging necrosis.In every group of infection groups,with the infection time,the deepening of the extent of fibrosis, interleukin-4,INF-γexpression in the liver changs.The most positive expressions were positioned in portal area,the vessel wall,fiber spacing between the cord and foreign giant cells,lymphocytes,cytoplasm of macrophages in the necrtic area of hepatic lobules,there were no positive signal in liver cells,interferon-γby Th1 cells secreted began to rise at 1~8weeks after infection,and reached the peak at 8 weeks,then decline.cytokines interleukin-4 by Th2 cells secreted increased rapidly at 12 weeks after infection and with time,the extension of infection increased significantly.[Conclusion]The extent of rats liver damage after infecting with Pagumogonimus skrjabini at the time of fibrosis had been deepened,with the deepening of the degree of liver fibrosis,the expression of interleukin-4,interferon-γwere changed,cytokines interferon-γ,with Thl cells secreting was closely related to induction and the formation of liver fibrosis in rats infected with Pagumogonimus skrjabini,and cytokines interleukin-4 by Th1 cells secreted can repress that Th1 cells secret cytokines,interleukin-4 by Th2 cells secreted plays an important role in spontaneous immune regulation of liver fibrosis in rats infected with pagumogonimus skrjabini. |