The Effect of Oleanolic Acid Combined with Tacrolimus on Th1/Th2 in Rats after Renal Transplantation

QIAN Kun; JIANG Hong-tao; ZHOU Hao

Abstract：Objective:To investigate the effect of Oleanolic Acid(OA) combined with Tacrolimus(FK506) on T helper cells(Th1/Th2) in rats after renal transplantation,and assess the possibility that OA synergizes FK506 based immunosuppressant,thus acting as an clinical immunosuppressive combination to promote renal allograft survival and function.Method:Renal allogenic grafting was performed on BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomly divided into four groups:control group(n=12),OA group(n=12),FK506 group(n=12),OA+FK506 group(n=12),and then interventions were made from 1 day before renal transplantation (RTx). Concentrations of serum creatinine in rats(n=6) were regularly examined and survival length of rats(n=6) were recorded in each group after RTx. In each group(n=6),concentrations of proinflammatory cytokines(IFN-γ,IL-2,IL-4,IL-6) were analyzed by Luminex, and also T-cell phenotypes(IFN-γ,IL-2,IL-4,IL-6) were analyzed by ELISpot on 5 days after RTx.Result:Renal allograft survival in OA+FK506 group was markedly prolonged as compared to other groups. A significant decrease in IL-2 was demonstrated in OA group and OA+FK506 group as compared to control group, meanwhile more significant decrease in that was demonstrated in OA+FK506 group. A significant decrease in IFN-γ,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant increase in that was demonstrated in OA+FK506 group. A significant decrease in frequencies of T cells secreting IFN-γ,IL-2,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant decrease in those was demonstrated in OA+FK506 group. A significant decrease in frequencies of T cells secreting IFN-γ,IL-2,IL-4 and IL-6 in administration groups was demonstrated as compared to control group,meanwhile more significant decrease in those was demonstrated in OA+FK506 group.Conclusion:OA and FK506 exert synergistic effect towards markedly inhibiting Th1/Th2 cells,decreasing rejection,and further enhancing renal allograft survival and function in rats. We hypothesized that novel therapeutic approaches involving combination of OA combined with FK506 will produce potential beneficial outcomes in clinical renal transplantation.