ABSTRACT
Objective To investigate the role of oridonin in preventing skin graft rejection.Methods BALB/c mice were transplanted with skin grafts from C57BL/6 mice.Grafted mice were treated daily with oridonin,CsA and PBS,respectively.The survival of grafts was inspected daily and evaluated by histological analysis.On day 7 after transplantation,the percentage of CD4+ CD25+ Foxp3+ cells (Treg) in the spleen was determined by flow cytometry.The effect of oridonin on MLR and apoptosis was examined in vitro.Naive BALB/c mice were intraperitonealy injected with oridonin (15 mg/kg/day).At different time points,the number of T cells and macrophages in peripheral blood mononuclear cells (PBMCs) as well as the spleen was examined.Results The survival of skin grafts in the oridonin group (15.8 ± 1.5 days) was significantly longer than that in the control group (12.3 ± 1.2 days) and the CsA group (13.3 ± 1.1 days).Oridonin reduced inflammatory cell infiltration in grafts.The expression of Tregs was higher in the oridonin group (17.6 ± 3.6％) than in the control group (14.8 ± 2.3％).In vitro oridonin inhibited MLR and induced apoptosis in a dose-dependent manner.The number of T cells in PBMCs was rapidly decreased following oridonin treatment.With the depletion of T cells in PBMCs,high frequency of granulocytes was observed.On day 8,the number of T cells in the spleen was decreased,which was accompanied by increased phagocyte number.Conclusion Oridonin could suppress allograft rejection and prolong survival of skin grafts.The mechanism may be attributed to upregulation of Tregs and clearance of T cells.