Protective Effect Of MG132on Ischemia Reperfusion Injury After Pancreasticoduodenal Transplantation In Rats

Objective:1. To modify the traditional techniques to establish a stable model ofpancreaticoduodenal transplantation（PDT） in rats，so as to improve thesuccessful rate and make a adequate preparations for the future studies.2. To investigate the effects of Proteasome inhibitor MG132onexpression of NF-ΚB and TNF-α、ICAM-1in rat pancreas with ischemiareperfusion injury(I/RI) after pancreas transplantation，and discuss themechanism of the procedure.Methods:1. Diabetes mellitus（DM） was induced in SD rats by a singleintraperitoneal injection of Streptozotocin (STZ) at dose of60mg/kg.Pancreaticoduodenal transplantation was adopted between normal SD rats asdonors and DM rats as recipients. Arterial reconstruction was performedbetween the donor’s aorta and the recipient’s aorta by end-to-sideanastomosis, while the donor’s portal vein was anastomosed with therecipient’s left renal vein by cuff technique. The proximal part of duodenum of graft was ligated and enterostomy was performed on the distant part.2.18normal SD rats were allocate into the sham operation（groupA）.The allogenic male SD rats model of pancreas transplantation. Therecipients were another2groups (n=18, in each) at random: I/R group(group B), MG132pretreatment group（group C）. Assay for serum amylasewas carried out at1,3and6hours after the operation in each group. Pancreassamples were harvested at the same time for pathological study by lightmicroscopy. The expression of NF-κB P65protein in pancreas was detectedby Western blot. The expression of TNF-α, ICAM-1in pancreas wasdetected by immunohistochemistry and RT-PCR.Result:1. A total of30operations were performed，and25of30rats survivedmore than3days with normal glucose. The success rate of operation was82.2%. Among30rats，the mean time of donor operation was（63.5±5.5）minutes while that of recipient was （55.0±5.0）minutes. The preparationof cuff consumed2minutes. The time spend on arterial reconstruction was（17.1±2.5）minutes，while that on vein reconstruction wa（s3.35±0.69）minutes. There was no hot ischemic time in graft, and the mean coldischemia time was(49.5±5.1)minutes.2. Tissue damage of group B was more severe than that of group A; Thelevel of serum amylase, the expression of P65,TNF-α and ICAM-1werehigher in group A than those of group A（P＜0.05）. Tissue damage of group C was more slight than that of group B; The level of serum amylase, theexpression of P65,TNF-α and ICAM-1were lower in group C than those ofgroup B（P＜0.05）.Conclusion：1. This type of PDT model in rats simplified the procedures of thetraditional operation，meanwhile lay the foundation for the related study.2. MG132can inhibit the activation of NF-κB in the procedure ofpancreas transplantation in rat, and the expression of TNF-α, ICAM-1willde decreased because of the inhibition effect. So it is a potential way torelieve the I/RI in pancreas transplantation by using Proteasome inhibitorMG132to inhibit the activation of NF-κB.