Role Of P-selectin And Intercellular Adhesion Molecule-1 During Ischemia/reperfusion Injury Of Rat Pancreas Transplantation

Objective Established the whole pancreaticoduodenal transplantation model in the rat with microsurgery technique to prepare for further pancreas transplantation related researches.Methods The diabetes mellitus SD rats induced by alloxan were used as recipients and healthy SD rats were used as donor.50 cases of whole pancreaticoduodenal transplantation in rats were done in official test.After operation,the general status of the rats and blood glucose levels were determined for the evaluation of the effects of whole pancreaticoduodenal transplantation on experimental diabetes.Results The success rate of the operation was 80%.The level of blood glucose of successful transplanted rats recovered to normal on the first day after operation and maintained normal during the period of observation.Conclusion The results indicated that whole pancreaticoduodenal transplantation could cure experimental diabetes mellitus.Second part Role of P-selectin and intercellular adhesion molecule-1 during ischemia/reperfusion injury of rat pancreas transplantationObjective To investigate the role of P-selectin(Ps) and intercellular adhesion molecule-1(ICAM-l) during ischemia/reperfusion injury of rat pancreas transplantation.Methods 75 Sprague-Dawley rats were randomized into transplanted group,therapeutic group and sham operation group.Both the transplanted group and thetherapeutic group rats received whole pancreaticoduodenal transplantation.In the therapeutic group monoclone antibodies(mAb) against P-selectin were applied before reperfusion.Sham operation group rats were anesthetized,laparotomized,resected left kidney and clamped the aorta below left renal vein for the same time with the transplanted group. Pancreas and blood samples of the three group rats were harvested at 1 hour(n=5),3 hour(n=5) and 6 hour(n=5) after releasing the clamp for immunohistochemistry analysis of P-selectin and ICAM-l,histopathology and serum amylase assay.Results (l)The damage of graft pancreas tissue was aggravated gradually as reperfusion was prolonged and was related to neutrophil infiltration,while these changes were mild in the mAb treated group.(2)Both Ps and ICAM-1 were expressed in the transplanted group,but were not expressed in the sham operation and the therapeutic group.The expression of Ps peaked at 1 hour after reperfusion and the expression of ICAM-1 was augmented gradually as reperfusion was prolonged.(3)The level of serum amylase has no marked change in sham operation group(/)>0.05) but was elevated markedly in transplanted group as reperfusion was prolonged(P<0.05),while it was ameliorated in the therapeutic group.The level of serum amylase was much higher in transplanted group than sham operation group(P<0.05) and therapeutic group(P<0.05).Conclusion (l)It resulted in ischemia/reperfusion injury in pancreas transplantation that neutrophil was activated and released various kinds of proteolytic ferment and active factors. (2)Ps and ICAM-1 may play important roles at the different stages of ischemia/reperfusion injury in rat pancreas transplantation.(3)Ps may be the initial factor during ischemia/reperfusion injury of rat pancreas transplantation.(4)Anti-Ps mAb has protection effect on ischemia/reperfusion injury of pancreas transplantation.