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

摘要

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-10 intragraft in recipients were measured on day 1, 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 100 days, 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+-41 U/L-360+-104 U/L, BIL 13+-5 mmol/l-38+-ll mmol/Ⅰ; vs Group Ⅱ, P<0.05; vs Group Ⅲ, P>0.05. Rejection activity index was significantly decreased (0-3.3+-1.6; vs Group Ⅱ, P<0.05; vs Group 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)2D3 induced 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.