动物造模,药效评价,肝移植 z-bio 2024-07-30 425

　　The graft-versus-host reaction is a rejection reaction that occurs when lymphocytes in the transplant recognize host antigens, become sensitized, proliferate and differentiate, and directly or indirectly attack the target tissue of the recipient. Due to the invasion of donor T cells into the epithelium, mucosa, bile ducts, and digestive tract of the skin, the main sites of lesions are in the skin, liver, and digestive tract. In addition, lesions can also occur in follicular cells, airways, bone marrow, and other tissues of hair follicles. Graft-versus-host disease (GVHD) mainly occurs after bone marrow transplantation, and is also seen in other immune organs or cell transplants, including spleen transplantation and blood transfusion. GVHD after human small intestine transplantation, liver transplantation, and kidney transplantation has also received attention in recent years.

　　The typical clinical manifestations of acute GVHD are rash, enterocolitis with diarrhea, liver dysfunction with jaundice, and fever. Our laboratory used the offspring of female Lewis rats and male BN rats as recipients, and male Lewis rats as donors. During liver transplantation, fresh 4X108 donor derived spleen cells were intravenously infused to establish an experimental model of acute GVHD (LTx aGVHD) after liver transplantation. All recipient rats exhibited typical aGVHD characteristics after surgery, and the final outcome was death, with an average survival of 23 days.

　　Simply replacing the liver of Lewis rats (LewisXBN) with the liver of F1 rats is not sufficient to produce aGVHD; However, when different numbers of donor spleen cells (1X108, 2X108, 3X108, 4X108) were transferred to the recipient with liver transplantation, the incidence rate of fatal aGVHD was 16.7%, 50%, 83.3%, and 100%, respectively. Clinical manifestations and histological analysis (skin and colon) exhibit typical characteristics of aGVHD. However, unlike transfusion associated aGVHD, there was no significant change in transplanted liver function. These clinical manifestations and histological analysis results of aGVHD are consistent with the characteristics exhibited by aGVHD after human liver transplantation.