Objective  To compare the modeling effect of chronic rejection following orthotopic and heterotopic intestinal transplantation in rats.

  Methods  F344 (RT1^1vr) rats were used as the donors and Lewis (RT1¹) rats were used as the recipients. Models of allogeneic heterotopic and orthotopic intestinal transplantation in rats (8 rats in each model) were established, and subcutaneous injection of ciclosporin was given at 0~14 d after operation. Changes in body weight and survival time of the recipients were observed after operation. In addition, pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Changes in collagenous fibers and elastic fibers in intestinal tissue were observed after alcohol and hematoxylin staining. Finally, success rate of modeling of recipients in two groups was calculated.

  Results  Rats in heterotopic and orthotopic intestinal transplantation groups were able to survive for a long time, most of which were more than 90 d. For the rats in orthotopic intestinal transplantation group, normal diet could be recovered at the 3^rd d after operation. Their body weight could recover preoperative level at about the 14^th d after operation, and then grew slowly. However, most of the rats in orthotopic intestinal transplantation group continued weight loss from the 150^th d after operation, which could not be reversed with ciclosporin. For the rats in heterotopic intestinal transplantation group, normal diet could be recovered at the 1^st d after operation, and their body weight could recover preoperative level within 25-30 d after operation and gradually rose and remained at a high level within 30-90 d after operation. No pathological changes of chronic rejection and obvious mesangial fibrosis in intestinal tissue were observed at the 90^th d after operation, but intestinal tissue developed chronic rejection and obvious mesangial fibrosis at the 163^rd d and 200^th d after operation in orthotopic intestinal transplantation group. Typical pathological changes of chronic rejection and mesangial fibrosis in intestinal tissue were observed at the 90^th d and 200^th d after operation for rats in heterotopic intestinal transplantation group. All the rats in heterotopic intestinal transplantation group showed characteristic pathological changes. The success rate of modeling was 100% in heterotopic intestinal transplantation group, which was not of statistical significance, compared with the success rate of modeling of 75% in the orthotopic intestinal transplantation group(P > 0.05).

  Conclusions  Chronic rejection will occur at different time points with small dose of ciclosporin after operation if models of orthotopic and heterotopic intestinal transplantation are established in combination of F344→Lewis rats. Compared with orthotopic intestinal transplantation, the rat model of heterotopic intestinal transplantation holds the advantages of simple modeling, shorter chronic rejection and relatively consistent degree of pathological changes, which is more suitable for experimental study.