Abstract:

Objective   To investigate expressions of regulation upon activation of normal T-cell expressed and secreted(RANTES) and CCR5 in the chronic rejection of cardiac allografts. Methods   Cervical cardiac transplantation by cuff-technique was performed from Wistar rats to Sprague-Dawley (SD) rats. The SD rat recipients were randomly divided into 3 groups: (A) (n=12) Both the recipients and the donors were without any treatment. (B)(n=12) The recipients were treated with 10mg/kg-1 cyclosporine A after transplantation and euthanized 2 to 3 months later. (C)(n=24) The Sprague-Dawley rat recipients were pretreated with donor splenocyte (SPC) and cyclophosphamide (CP). Half were euthanized 15-60 days after transplantation(C1) and the other half were monitored for at least 6 months after transplantation(C2). Pathological change of the allograft caused by the rejection was observed by H-E staining. Cardiac allograft vasculopathy (CAV)was observed by Van Gieson staining. Expressions of RANTES and CCR5 were monitored by immunohistochemistry.  Results   Pretreatment of animals with SPC and CP induced long-term cardiac allograft survival. Immunohistochemical staining demonstrated a low level of RANTES and CCR5 expressions in the cardiac allograft muscles and coronary arteries in Group C. In contrast, expressions of RANTES and CCR5 in the cardiac allografts of Groups A and B were significantly higher than those in Group C (P<0.05). The CAV and myocardial fibrosis were dramatically reduced in Group C compared with those of Groups A and B (P<0.05).  Conclusion   Expressions of RANTES and CCR5 in cardiac allografts may play an important role during the development of chronic rejection.

Key words:  Cardiac allograft vasculopathy； Myocardial fibrosis； Chemokine and chemokine receptor； Rats