Oleanolic acid synergizes with cyclosporine A to prolong renal allograft survival in rats

QIAN Kun; LIAO Wenting; LI Jianjun; JIANG Hongtao; ZHOU Hao; LONG Jianhua; QIN Guoqing; WANG Yi

doi:10.3969/j.issn.1673-4254.2014.06.18

Abstract：Objective To investigate the synergistic effect of oleanolic acid (OA) and cyclosporine A (CsA) on the survival of renal allografts in rats. Methods Renal allograft transplantation was performed using BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomized into 4 equal groups for interventions with DMSO-PBS (control), OA, CsA, or CsA+OA, starting from 1 day before transplantation. Serum creatinine levels were regularly examined, and the survival of rats were recorded. On day 5 after transplantation, CD4 + and CD8 + T-cell infiltration in the renal grafts was analyzed by immunohistochemistry; the concentrations of the proinflammatory cytokines (IL-1β, IFN-γ, IL-2, IL-4, and IL-17), anti-inflammatory cytokine IL-10 and chemokines (IP-10, MCP-1, MIP, and Mig) were analyzed with Luminex; the T-cell phenotypes (IFN-γ, IL-10, IL-4, and IL-17) were analyzed using ELISpot. Results In OA+CsA group, renal allograft survival was markedly prolonged and CD4 + and CD8 + T cell infiltration in the graft significantly decreased as compared to other groups. A significant decrease in IL-2 was observed in OA group and OA+CsA group, especially the latter. Compared with the control group, all the 3 treated groups showed significantly decreased IL-1β, IP-10 and MCP-1, increased IL-10 levels, decreased percentages of T cells secreting IFN-γ, IL-4 and IL-17, and increased percentage of T cells secreting IL-10. The increments of serum IL-10 level and T cell percentage were more prominent in OA+CsA group than in the other two intervention groups. Conclusions OA and CsA synergistically ameliorate renal graft rejection and inflammation and promote allograft survival and function in rats.