Effect Of P38 MAPK In Acute Rejection After Cardiac Transplantation And Inhibited By Tacrolimus

Objectives: To investigate the expression of p38mitogen activated protein kinase (p38 MAPK) and therelation with apoptosis and tumor necrosis factor- a (TNF-a ) expression in cardiac grafts during cardiac acute allograftrejection, further study the effect of tacrolimus (FK506).Medthods: The rat model of heterotopic cardiac transplantation was developed. The rats were divided into the following groups: control group of cardiac isograft of SD to SD rats, group of cardiac allograft of wister to SD rats and FK506-treated group of cardiac allograft. The grafts were collected at Id, 3d, 5d and 7d after operation to receive histopathological examination and apoptosis of cardiac cells was examined by terminal deoxynudeotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL), the number of p38 MAPK/CD8+ double positive cells in grafts was analyzed by a laser scanning control imaging system, the expression of p38 MAPK in grafts was detected by Western blot, the TNF- a mRNA expression in grafts was examined by reverse transcription polymerase chain reactions (RT-PCR).Results: Compared with control group, the amount of apoptosis cells, the expression of TNF- a and p38 MAPK, the number of CD8+/p38 double positive cells in cardiac allograft of BN to LEW without immunosuppression significantly increased (PO.OOl) during the same period (5d and 7d) after the operation. The increase was reversed by FK506.Conclusions: In allogeneic group without immunosuppression. the amount of apoptosis cells, the number of CD8+/p38 double positive cells, the expression of TNF- a and p38 MAPK all increased during the same period, which suggest that intragraft expression of p38 would be associated with the rejection in cardiac acute allograft rejection. FK506 may alleviate the rejection partly by inhibiting p38 MAPK.