Title: Early adoption a chemokine receptor antagonist Met-RANTES suppressing acute rejection of small bowel allograft in rats
Abstract: Objective To explore the immunosuppression effect of early adopting Met-RANTES after small bowel transplantation on allograft rejection and its synergic effect with tacrolimus. Methods In mature male SD rats as donors and Wistar rats as recipients, the model of heterotopic segmental small bowel transplantation was set up. Rats were divided into 4 groups after transplantation, and each group had 24 rats: group 1 , allogeneic small bowel transplant untreated group as control group; group 2 , allogeneic small bowel transplant treated with Met-RANTES (200 μg/day, i.p, 0~ 7 days); group 3 , allogeneic small bowel transplant treated with low dose of tacrolimus (FK506, 0.5 mg·kg~ -1 ·day~ -1, i.p, 0~7 days); group 4 , allogeneic small bowel transplant treated with Met-RANTES and FK506 in the same way with group 2 and 3. After transplantation clinical course, survival time and immuocyte infiltration were observed. Grafts (n=6) of each group were sampled respectively at day 3, 5, and 7 after the transplantation. All samples were examined pathologically. By using immunofluorescent staining and laser scanning confocal microscope techniques, successive quantitative measurement was conducted to detect the expression of graft RANTES and CD4~ +, CD8~ +, CD25~ + T lymphocytes. Results Average survival time in groups 1, 2, 3 and 4 was ( 7.37± 1.19) days, ( 22.32± 8.60) days, ( 23.64.32± 6.58) days, and ( 30.55± 4.18) days. Compared with that in the group 1, the average survival time in groups 2, 3 and 4 was obviously prolonged (P 0.01). The average survival time in group 4 was much longer than that in groups 2 and 3 (P 0.01). Rats in group 1 died of acute rejection and infection. The histological examination revealed that in the first group mild, moderate and severe rejection occurred on the post-operative day 3, 5, and 7. While in groups 2, 3 and 4, no obvious rejection occurred. The RANTES expression in group 1 in each postoperative period was significantly higher than that of the other three groups (P 0.01). There was a positive correlation between the dynamic change of the RANTES expression and the process of acute rejection. The CD4~ +, CD8~ +, CD25~ + T lymphocytse and the RANTES expression of the grafts in groups 2 and 4 were significantly lower than in group 1 (P 0.01).Conclusions Met-RANTES may obviously suppress acute allograft rejection in small bowel transplantation, effectively protect the function of grafts, and significantly prolong the survival time of the recipients. In addition, Met-RANTES may enhance the immunosuppressive function of FK506 with low dose.
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
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