动物造模,肝移植慢性排斥反应模型 z-bio 2021-04-12 745

　　Chronic rejection mostly occurs several months after liver transplantation. It has been reported that it appears in the first month after transplantation. It is gradually aggravated and liver function gradually deteriorates. Generally, it shows irreversible changes. It is the main cause of loss of function of transplanted liver in the later stage of transplantation. The reason is also the main reason that affects the long-term healthy survival of patients. The clinical manifestations are progressive cholestasis, increased bilirubin, and increased alkaline phosphatase. The transplanted liver often enlarges and hardens. The pathological manifestations of the liver include destruction of the interlobular bile duct, progressive fibrosis, disappearance of cell infiltration in the portal area, fibrosis of the vascular intima, and sometimes foam cells.

　　Different strains of rat liver transplantation have not been found to have clinically similar models of chronic rejection. The acute liver transplant rejection model formed by the combination of Fisher 344→Lewis or DA→BN rat strains is commonly used to establish an experimental model of chronic liver rejection after drug induction.

　　Our laboratory uses DA rats as donors and BN rats as recipients for orthotopic liver transplantation. Continuous subcutaneous injection of cyclosporine A (lmg/kg/d) 1 to 30 days after surgery has successfully established rat livers. Transplant chronic rejection model. Chronic rejection occurs within 30 to 60 days after surgery, and the median survival time is 58±14.93 days. Two months after the operation, the pathological examination revealed that there were obvious lymphocytes, neutrophils and eosinophils and other inflammatory cells in the graft. At the same time, bile duct hyperplasia and bile duct damage were also obvious, and the bile duct epithelium was focal. The necrosis exceeds 50%, and some bile ducts disappear completely or become fibrotic. The liver structure changes from the structure of liver lobules to the tissue structure mostly composed of nodules and fibers. Residual liver cells showed degenerative disease and necrosis, and there were complete and incomplete fibrous partitions in the junction of the portal area. Different degrees of fibrocyte and inflammatory cell deposition can be seen in the arterial wall, the vascular occlusion range exceeds 50%, and some arteries are completely blocked or fibrotic.

　　The chronic rejection model of rat liver transplantation is generally used to study the mechanism of chronic rejection after liver transplantation, preventive measures, and the application of immunosuppressive agents.