Objective To summarize the advancement of immune tolerance in pancreas transplantation.Methods Relevant literatures about immune tolerance in pancreas transplantation, which were published recently domestic and abroad were collected and reviewed. Results The main methods to induce immune tolerance are peripheral tolerance and central tolerance. The induction of chimerism by infusion of donor-specific bone marrow cells is the research hot spot recently. Conclusion The infusion of donor-specific bone marrow cells in combination with one or more peripheral tolerance maybe can induce immune tolerance successfully. However, it should be researched further.
ObjectivesTo explore the mechanisms by which ischmic preconditioning (IPC), ischemic postconditioning (IPO) and IPCIPO exert influence on ischemic reperfusion injury (IRI) of the graft of SD rat after pancreas transplantation. MethodsAfter the establishment of diabetic SD rats model by using streptozotocin, 24 rats suffered from pancreas transplantation and were randomly averagely divided into four groups: I/R group, IPC group, IPO group, and IPC-IPO group. Six diabetic SD rats suffered with sham operation were served as SO group. The blood glucose level of rats in each group was detected before and after reperfusion, the contents of malonaldehyde (MDA) and super oxide dismutase (SOD) of pancreas allograft were tested at 2 h after reperfusion, and the apoptosis index (AI) of pancreas allograft was monitored by using TUNEL method. ResultsThe blood glucose level of rats in each group was not significantly different (Pgt;0.05). In SO group, the blood glucose level of rats was significantly higher than other groups (Plt;0.01). The blood glucose levels of rats after reperfusion decreased from the levels before reperfusion in I/R group, IPC group, IPO group, and IPC-IPO group (Plt;0.05 or Plt;0.01), furthermore the blood glucose level of rats in I/R group was significantly higher than that in abovementioned three groups (Plt;0.01), although among which the difference was not markedly (Pgt;0.05). When compared with I/R group, the MDA contents of rats after reperfusion in IPC group, IPO group， and IPC-IPO group decreased (Plt;0.01), while the SOD contents of rats after reperfusion increased (Plt;0.01). In rats of SO group, the MDA and SOD contents were significantly higher and lower than other groups, respectively (Plt;0.01). The MDA and SOD contents in IPC group, IPO group, and IPC-IPO group were not different (Pgt;0.05). The AI of pancreas allograft at 2 h after reperfusion in I/R group 〔(47.31±4.52)%〕, IPC group 〔(26.25±3.17)%〕, IPO group 〔(24.73±3.62)%〕, and IPC-IPO group 〔(25.5±4.15)%〕 were higher than that in SO group 〔(3.16±0.53)%〕, Plt;0.01. The AI of pancreas allograft in IPC group, IPO group, and IPC-IPO group were not different (Pgt;0.05), but they were lower than that in I/R group (Plt;0.01). Pathological results showed that injury of pancreas allograft in I/R group was most severe. ConclusionsIPO and IPC are associated with comparable effectiveness to protect graft from IRI during pancreas transplantation. The combined protective effects of IPC and IPO do not appear to be additive, which is equal to IPC or IPO alone.
Objective To investigate the roles of cell apoptosis and the gene expressions of Fas, FasL, bcl-2 and bax in acute rejection of pancreaticoduodenal transplantation and to evaluate the function of duodenum biopsy for early detection of rejection in rats. Methods Wistar and SD rats were divided into two groups: ①Wistar rats that underwent allogenic pancreaticoduodenal transplantation from the organs of SD rats; ②Wistar rats that received homogenic transplantation. The grafts were then harvested on day 3, 5 and 7 after the transplantation, and all graft samples were observed with HE staining and TUNEL was also used to detect apoptotic cells. The expressions of Fas, FasL, bcl-2 and bax were measured by immunochemical method. According to Nakhleh’s score, pathologic features of transplanted pancreas and duodenum were ranged from one to three scores in order. Results The percentage of same or different scores between the pathological scores of pancreas and duodenum in allogenic pancreaticoduodenal transplantation group were 61.1% (11/18) and 38.9% (7/18) respectively, and there were 6 specimens of pancreatic tissue got higher scores with only one higher score for duodenum. There were significant differences of histopathologic rejection scores and apoptotic indices between the two groups, respectively (P＜0.05， P＜0.01). Apoptotic indices of pancreas and duodenum both showed positive correlations with histopathologic rejection scores (r=0.965， P＜0.01; r=0.942, P＜0.01). The rejection score and apoptotic index elevated, the expression of FasL increased, bcl-2 decreased, and Fas and bax changed over time after operation. Conclusion Apoptosis maybe significantly positive correlated with the degrees of damage of the acute pancreaticoduodenal allograft rejection, and the apoptotic index maybe valuable to estimate the damage. FasL and bcl-2 were significantly related to the impairment of acute pancreatic allograft rejection as well. Duodenum biopsy may contribute to the early diagnosis of the rejecting transplanted tissues.
ObjectiveTo explore apoptosis of acinar cells during pancreatic allograft rejection in rats.MethodsGroups of Wistar rats underwent heterotopic pancreaticoduodenal transplantation from syngenic Wistar of allogenic SD rats. The grafts were harvested on postoperative day 3, 5 and 7. All graft samples were subjected to histological examination and apoptotic cells of graft acinar cells using in situ terminal deoxynucleotidy1 transferasemediated dUTP nickend labeling (TUNEL). Histopathological rejection score and apoptotic index (AI) were analyzed. ResultsThe incidence of apoptotic cells was increased steadily over time in allografts, in contrast with syngenic grafts. The apoptotic cells in allografts were mainly acinar cells and few infiltrating lymphocytes. A significant correlation between apoptotic index and histopathological rejection score was noted.ConclusionTUNEL can display apoptosis of single cell in situ. Apoptosis is an important mechanism of tissue injury in acute pancreatic allograft rejection in rats. Acinar cell apoptosis can be used as a valuble index to estimate the injury of grafts and to monitor the acute rejection.
【Abstract】Objective To investigate the effect of donor blood transfusion on inducing pancreatic allograft tolerance in outbred rat model. Methods Wistar male rats were used as blood and pancreas donor, and diabetic recipients. One ml of donor blood injected into abdomen of diabetic recipients on the day of transplantation and azathioprine given 2 days pretransplant and continued for three days. Results Pancreas allograft survival was significantly prolonged (28 to 112 days, media survival time 64.2 days). One ml of donor blood alone injected into the abdomen and azathioprine given alone 2 days pretransplant did not improve allograft survival (media survival time 9.8 vs 10.2 days). Conclusion Donor blood injected on the day of transplantation and a 3 days course of azathioprine started 2 days pretransplant have b synergism in inducing long term graft survival in this rat model.
Objective To evaluate the efficacy and safety of prophylactic octreotide for preventing complications after pancreas transplantation. Methods We searched The Cochrane Library (Issue 1, 2008), PubMed (1970 to January 2008), EMbase (1974 to January 2008) and CBM (1978 to January 2008). Six studies concerning prophylactic octreotide in preventing complications after pancreas transplantation were retrieved. Study selection and assessment, data collection and analyses were undertaken by two reviewers independently. Meta-analyses were done using The Cochrane Collaboration’s RevMan 4.2.10 software. Results Three RCTs, involving a total of 82 patients were included in the review. On the fifth postoperative day, the urinary amylase was significantly lower in patients in the octreotide group compared to the control group (SMD=–784.86, 95%CI –1464.24 to –105.49, P=0.02), and no significant difference was observed between the two groups in serum amylase (SMD=–12.26, 95%CI –56.53 to 32.06, P=0.59). No significant difference in the incidence of complications was noted between the two groups. The differences between the two groups in graft survival rate (90 days after operation) and patients’ 6-month survival rate were not statistically significant (RR=0.96, 95%CI 0.83 to 1.11, P=0.56; RR=1.17, 95%CI 0.86 to 1.58, P=0.32, respectively). As for safety, there were no reports of adverse effects of octreotide on CsA or FK506 absorption and no reports of other adverse reactions. Conclusion The evidence currently available shows that prophylactic octreotide is not capable of reducing dramatically the occurrence of pancreatitis, fistula, thrombosis and rejection after pancreas transplantation. And there is no obvious influence on graft survival rate and patient survival rate. Because the RCTs available for this systematic review are too small, further high-quality large-scale RCTs with long-term follow up are required to provide more reliable evidence.
【Abstract】ObjectiveTo discuss the technique for pancreas transplantation alone(PTA). MethodsEighty-eight SD rats were used as donors and recipients. The PTA was performed with enteric drainage（E-D group, n=22） or bladder drainage（B-D group, n=22）. The donor’s abdominal aorta(splenic artery) and portal vein(splenic vein) were anastomozed with the recipient’s abdominal aorta(end-to-side) and left renal vein(end-to-end). Blood glucose, food intake, water intake and urine volume were recorded before transplantation and on the 1st day, 3rd day, 7th day, 14th day and 30th day after transplantation. Results The mean PTA time was (33.1±11.1) min (donors) and (51.7±14.7) min(recipients). The grafts experienced no warm ischemia and the mean cold ischemia time was (46.5±17.1) min. After the successful PTA, the recipients’ blood glucose decreased on the first day after transplantation and reached normal on the third day. Their food intake, water intake and urine volume decreased and became stable 14 days later. ConclusionSuccessful PTA can restore the pancreatic endocrine function in diabetic rats. It is very important to master the technique for the operation.
胰腺移植主要包括单独胰腺移植（pancreas transplantation alone, PTA）、肾移植后胰腺移植（pancreas after kidney transplantation, PAK）和胰肾联合移植（simultaneous pancreaskidney transplantation, SPK）。与其它实体大器官移植一样，胰腺移植成功的真正转折始于20世纪70年代末。随着新型免疫抑制剂的开发和应用、器官保存技术的改进和外科技术的日臻成熟，胰腺移植在全球范围内得到迅猛开展，胰腺移植受体及器官存活率显著提高。据国际胰腺移植登记中心（International Pancreas Transplant Registry, IPTR）记录，至2001年10月，全球已实施17 000余例胰腺移植，其中美国有11 500余例，胰腺移植后患者1年生存率超过95%，3年生存率接近90%； 移植胰腺1年和3年有功能生存率分别为83%和77%［1，2］。自1966年首例SPK在美国Minnesota大学成功实施以来，SPK已成为治疗Ⅰ型糖尿病合并肾功能衰竭的常规方法，全世界迄今为止已实施的胰腺移植中约90%采用该术式［3，4］。
【Abstract】Objective To investigate the effects of preservative temperature on pancreatic function and determine the optimal preservative temperature for pancreatic transplantation. MethodsCold pancreatic preservation was performed and a homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was established. The pancreas was preserved for 6 h in UW solution at specific temperatures(0 ℃, 4 ℃, 8 ℃ and 12 ℃). After preservation, pancreatic tissue was taken for histologic examination in every group. ATP and total adenine nucleotides (TAN) were determined by using high performance liquid chromatography (HPLC). Blood glucose(BG), serum amylase and lipase were measured 24 h after transplantation. And the activity of myeloperoxidase (MPO) in the pancreatic grafts was also measured at the same time. Besides, histological observation was performed. Results Microscopic studies showed that the histomorphological changes of pancreas in 4 ℃ group were less obvious than those in other groups. Tissual concentrations of ATP and TAN decreased gradually in 4 ℃ group, 0 ℃ group, 8 ℃ group, and 12 ℃ group after 6 h of preservation(PH＜0.05). The levels of BG, serum lipase and MPO increased gradually in 4 ℃ group, 0 ℃ group, 8 ℃ group, and 12 ℃ group(PH＜0.05). The activity of MPO in 4 ℃ group （1.19±0.16 U/g ）was significantly lower than that of the control group（0.26±0.09 U/g，PH＜0.05). Conclusion The temperature of 4 ℃ is most appropriate for hypothermic pancreatic preservation and can considerably alleviate cold ischemic injury of rat pancreas.
【Abstract】ObjectiveOn the basis of traditional transplantation model, a successful model of pancreaticoduodenal transplantation (PDT) were established in rats, which is the foundation of basic and clinical transplantation research. Methods We improved the technique of microoperation on donor and harvested high-quality graft. The dual cuff technique was applied to end-to-end anastomose proximal part of abdominal aorta and portal vein with left renal aorta and vein of recipient, and distal part of abdominal aorta was connected with Y-tube. External secretion was performed by duodenum stoma. The PDT model was finished without blocking systemic circulation and portal vein system. Random blood glucose levels and drainage were monitored postoperatively to evaluate the function of endocrine and ectocrine. Results Thirty operations were done. The total procedure of transplantation lasted 2 hours. Moreover the operation on recipient and the reconstruction of vessels took only (26±5) and (25±5) minutes, respectively. The success rate was elevated to 100%. The ectocrine function was restored within 2 hours after operation. Except for 3 cases of non-function graft because of thrombosis in cannula, the glucose level of the remaining recipients was reduced to normal level 6 h or 24 h after transplantation. The survival rate of graft function was 90% (27/30). Conclusion This model is finished without special equipment and can recover the endocrine function in advance. It is a simple and stable model, which might be used in research of the theoretical problems involved in clinical pancreas transplantation.