Effect of cyclosporine A versus tacrolimus on chronic allograft rejection following orthotopic small bowel transplantation in rats

Abstract

Objective To establish two models of long-term chronic allograft rejection (CR)following orthotopic small bowel transplantation and compare the two models induced by cyclosporine A (CsA) or tacrolimus (Tac).Methods F344 and Lewis rats severed as donors and recipients,respectively.Transplantation was performed by anastomosing the graft superior mesenteric artery to the recipient infrarenal aorta and the graft portal vein to the recipient infrarenal inferior vena cava in an end-to side fashion.The recipients intestine was replaced with the graft by performing end-to-end small bowel anastomosis.In the study I,the rat was given intramuscularly CsA (5 mg · kg-1 · day-1) from postoperative day (POD) 0 to 13; In the study Ⅱ,the rat was given intramuscularly FK 506 at a dose of 0.3,0.5 and 1.0 mg· kg-1 · day-1 on POD 0-13,20,27,respectively.The body weight gain,survival rate and histology were observed.Results In the study I,there were significant changes of the CR histologically,including villous architecture,interstitial fibrosis,leukocyte infiltration,and obliterative arteriopathy.There was no significant difference in features of CR between POD 60 and POD 90,however,the serious villous blunting was not found; In the study II,the rats received Tac at dose of 0.3 and 0.5 mg·kg-1 ·day-1 and survived up to POD 126.The recipients received Tac at dose of 1.0 mg·kg-1 · day-1 and survived more than POD 180 and the body weight gain was the same as the isogenic groups.The histopathological analysis revealed distinctive features of CR including villous blunting.The characteristics of CR induced by CsA or Tac in the rat model of orthotopic small bowel transplantation could be demonstrated,however,the Tac-induced model was more closer to clinical small bowel transplantation pathology of CR.Conclusion Using the protocol of CsA or Tac,we developed a rat CR model of orthotopic small bowel transplantation,however,the Tac-induced recipients survived longer and had more classic characteristics of CR than CsA. Key words: Small intestine transplantation; Graft rejection; Immunosuppressive agents; Disease models, animal