Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotoic liver transplantation

AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group Ⅰ: syngenic control (Wistar to Wistar); Group Ⅱ: acute rejection (SD to Wistar);Group Ⅲ: acute rejection treated with cyclosporine A, and Group Ⅳ: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-γ, IL-10intragraft in recipients were measured on day t, 5, 7, 15,30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.RESULTS: Survival time of recipients in Group Ⅳ was significantly prolonged (4/6 recipients survived for over 100days. vs Group Ⅱ, P＜0.001; vs Group Ⅲ, P＞0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group Ⅳ was significantly improved (AST 127±41U/L-360±104 U/L, BIL 13±5 mmol/1-38±11 mmol/l; vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05. Rejection activity index was significantly decreased (0-3.3±1.6; vsGroup Ⅱ, P＜0.05;vsGroup Ⅲ, P＞0.05). Level of hepatic IFN-γ, mRNA in group Ⅳ was decreased, while level of hepatic IL-10 mRNA was increased (vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05).CONCLUSION: Our results indicated that 1,25-(OH)2D3induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.