Objective  By reproducing mouse to rat heart xenograft

to determine the effect of leflunomide on NF-κB P65 in the transplanted heart.   Methods  The recipient rats were randomly divided into 4 groups: group A (n=6) receiving no immunosuppressant as control; group B (n=6) cyclosporine (CsA); group C (n=6) leflunomide (Lef)

group D (n=6) Lef plus CsA. The expressions of NF-κB P65 protein and NF-κB P65 DNA binding activity in transplanted heart tissues were determined by immunohistochemistry

Western blot and electrophoretic mobility shift assay (EMSA).   Results  Administration of CsA alone had no appreciable effect on the survival time of xenografts [(2.50±1.05) d] and could not suppress the protein expression of NF-κB P65 [(263.09±28.81)

IOD] and NF-κB P65 DNA binding activity [(227.49±14.83)

IOD] in the tissues of xenografts. Administration of Lef alone could significantly prolong the survival time of xenografts [(4.17±1.33) d] and could suppress the protein expression of NF-κB P65 [(173.48±585)

IOD] and NF-κB P65 DNA binding activity [(109.96±12.46)

IOD] (P0.05

vs group A and group B respectively). Lef plus CsA could significantly prolong the survival time of xenografts to (6.50±2.56) d and suppress the protein expression of NF-κB P65 [(67.79±3.79)

IOD] and NF-κB P65 DNA binding activity [(43.61±7.42)

IOD] (P0.05

vs group A

B and group C respectively).    Conclusion  Combination of Lef and CsA can significantly prolong the survival time of xenograft through suppressing the protein expression of NF-κB P65 and NF-κB P65 DNA binding activity in the tissues of transplanted hearts and exerts synergistic immunosuppressive effect in mouse to rat cardiac xenograft.