Establishment And Improvement Of Rat Liver Transplantation Model And Comparison On Transplantation Rejection In Various Strain Combinations Of Rats

Background and Objective Construction of stable and typical animal model is foundational for research on liver transplantation.Orthotopic liver transplantation in rat is one of the most widely used models in this field.The objective of this study is to construct a modified rat liver trans-plantion model and explore the optimum acute rejection models of various strains combination of rats,meanwhile detect the expression of T-cell subsets during acute rejection.Methods Orthotopic liver transplantation model in rat was constructed by using Kamada's two cuff technique without arterial reconstruction.Operation was modified during the seperation,harvest,perfusion,implantation of donor liver and nursing was improved after operation.Subsequently,four transplantation models of various strain combinations were established including the control group SD(donor) to SD(recipient) and the experimental groups Wistar to SD,Lewis to BN and DA to Lewis.And then a typical and optimum model of acute transplantation rejection was chosed by comparing the recovery state,survial time,liver function test and pathology examination.Finally,the expression of T-cell subsets were detected and evaluated by Flow cytometery,including CD3~+,CD3~+CD4~+,CD3~+CD8~-,CD4~+CD25~+,NKT in the recipient udergoing the severe acute rejection.Resuluts The modified rat liver transplantation model was established which was easier and more stable than our preliminary experiment.And rats recovered from operation bctter than before.Control group syngeneic rat SD to SD liver transplantation was tolerant and the immunological rejection in experimental group Wistar to SD was mild and indeterminate.In contrast,both experimental groups allogeneic rats Lewis to BN and DA to Lewis could induce obvious acute transplantation rejection,however the rat strain combination DA to Lewis is most typical and optimum acute rejection model.Compared with the transplantation tolerance group,in acute rejection group T-cell subsets CD3,CD4 and CD3~+CD 4~+/ CD3~+CD8~+ of the peripheral blood is higher,meanwhile natural killer T cells in the mononuclear cells of spleen and lymph node is lower,however there was no signifiance of T-cell subsets CD4~+CD25~+.Conclusion The experimental model we modified is easy and feasible.According to our results,the rat strain combination DA(donor) to Lewis(recipient) is a typical acute transplantation rejection model.The up-regulation of effector T-cell subsets CD3~+CD4~+ and the CD3~+CD4~+/CD3~+CD8~+ ratio and the down-regulation of NKT regulatory T cells may be associated with acute liver transplantation rejection in rats. This study started an effective beginning to explore the mechanism of rat transplantation rejection and the induction of transplantation tolerance.