| Objectives1. To master the way of setting up the model of segmental small bowel transplantation heterotopically in rats.2. To study the relationship between the expression of RANTES and acute rejection of allograft in different period after rat small bowel transplantation; and discuss the significance of the change of the expression of RANTES in early diagnosing allograft rejection.3. To investigate the effect of early adopting Met-RANTES in post-operation of small bowel transplant on rat allograft; and explore the immunosuppressive effect of chemokine receptor antagonist in allograft rejection in rat small bowel transplantation and the coordinative effect with FK506.Methods1. Heterotopic small bowel transplant was carried out between inbred mature male SD and Wistar rats. All recipients were divided into five groups and each group contains 24 rats. Group 1, SD; Group 2, SD-SD; Group 3, SD-Wistar; Group 4, SD-Wistar+ Met-RANTES(200 g d-1, ip); Group 5, SD-Wistar+Met-RANTES (200 g d-1, ip)+FK506 (0.5 mg kg-1 d-1, im). The grafts were sampled on the postoperative day 3, 5, 7 and hematoxylin eosin staining was conducted on the specimens (n=6) to observe pathological change.2. Successive quantitative measurement was conducted to detect the expression of intragraft RANTES, CD4+, CD8+ and CD25+ T lymphocyte with Immunofluorescent Staining and Laser Scanning Confocal Microscope Technique.3. Observations on post transplant clinical course and survival duration and immunocyte infiltration were recorded on allogeneic small bowel transplant untreated group and treated groups.Results1. The pathological examination of grafts in Group 3 demonstrated the mild, moderate, and severe rejection on postoperative day 3, 5, and 7 while rats in the Group 2, 4, and 5 showed no obvious indication of rejection.2. RANTES Expression of grafts in Group 3 was significantly higher than that of the other four groups (P<0.01) in every period. The dynamic change and the process of acute rejection showed positive correlation. The expression of intragraft RANTES, CD4+, CD8+ and CD25+ T lymphocyte in Group 4 and 5 are significantly lower than that in Group 3 (P<0.01).3. Compared with the survival duration of rats in Group 3, the survival duration of rats in Group 4 and 5 is significantly longer (P<0.01). And there is great difference in the survival duration between rats in Group 4 and rats in Group 5(P<0.01). Conclusion1. The dynamic observation on expression of intragraft RANTESmay act as a relatively sensitive predicator for diagnosing acute allograft rejection.2. The positive expression of RANTES and its control of the directional movement of immunocyte play an important role in the happening and development of acute allograft rejection. The degree of expression of RANTES may reflect the severeness of T lymphocyte infiltration. Therefore, measurement of the change in expression of intragraft RANTES may be the guidance of early diagnosing acute allograft rejection.3. RANTES and its receptors mediated cellular immunity are the essential components of acute allograft rejection. Specific blocking RANTES and its receptors signal conduction are of great significance in induction of grafts immune tolerance.4. Met-RANTES may obviously suppress acute allograft rejection, effectively protect the function of grafts, and significantly prolong the survival duration of the recipients. In addition, Met-RANTES may enhance the immunosuppressive function of FK506 with low dose. |
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