Objective To establish the model of pancreatoduodenal allotransplantation in pigs with enteric drainage (ED) and portal venous drainage (PVD). Methods Forty-six hybrid landraces were divided into two groups (donor and recipient groups) randomly, for pancreatoduodenal allotransplantation. Donors were perfused via abdomial aorta without clamping the portal venous outflow with UW solution after heparinization. Whole pancreatoduodenal graft was arvested with segments of abdomial aorta and portal vein and shaped under cold UW solution. Then, the end-to-end nastomosis was performed with the donor iliac artery bifurcation “Y” graft to the recipient superior mesenteric arteries and celiac artery. Furthermore, type Ⅰdiabete model was made by removal of the recipient pancreas. The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Meanwhile, the end-to-side anastomosis was performed with the donor common iliac artery bifurcation “Y” graft to the recipient abdomial aorta and the side-to-side intestinal anastomosis was performed between the donor duodenum and the recipient jejunum. External jugular vein was intubated for transfusion. The levels of blood glucose， insulin and glucagon in blood were measured before and during the operation and 1， 3， 5， 7 d after operation. Results Twenty-three cases of pancreatoduodenal allotranplantations were performed on pigs. One died from complication of anesthesia. Success rate of operation was 95.7％.Complications of operation happened in 2 cases in which one was phlebothrombosis, incidence 4.5％and the other was duodenojejunal anastomotic leak, incidence 4.5％. The level of blood glucose increased within 30 min and recovered on the 2nd day after removal of pancreas. The levels of insulin and glucagon decreased within 30 min and recovered on the 2nd day after removal of pancreas. Rejection curred at the 1st day and reached the worst level on the 9th day after transplantation without the change of insulin and glucagon in blood and clinical symptoms of rejection. Conclusion Pancreatoduodenal transplantation in pigs can treat type Ⅰ diabete. ED and PVD can keep the function of endocrine in normal. The technique of duodenal transplantation with ED and PVD may pave the way for the further development of pancreas transplantation in clinic.
OBJECTIVE To investigate the mechanism of xenotransplantation rejection and the interaction between the immunocytes. METHODS: This review concluded the research achievements and new advances in xenotransplantation based on the relevant experimental data. RESULTS: Transgenic pig technology and novel immunosuppressants were applied to suppress hyperacute rejection and acute vascular rejection respectively. Modulation of T cell and antigen presenting cells and induction of tolerance were taken for the prevention of acute cellular rejection. CONCLUSION: In general, the technology of transgenic pig is relatively mature and effective. The mechanism and prevention of acute vascular rejection and acute cellular rejection should be further investigated.
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.
【Abstract】Objective To evaluate the pathological diagnosis of liver allograft rejection. Methods Literatures about diagnosis of liver transplantation rejection in recent ten years were reviewed.Results Humoral rejection was rare. The main features were graft blood vessel thrombosis and liver damage and necrosis about some days or one week after transplantation. The humoral rejection of liver graft occurred later than that of kidney and heart transplantation. The diagnosis of acute liver graft rejection was based on Banff Schema. During chronic rejection intrahepatic bile ducts among hepatic lobules in portal area disappeared, and inflammation, fibrosis and stricture of hepatic arteries and veins were found, but the morbidity was less than that of kidney， heart, lung and pancreas grafting. Conclusion Banff standard is the most important base of diagnosing liver graft rejection.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
Objective To investigate the effect of nidus vespae on lymphocyte blastisation in mixed culture system of lymphocyte and pancreatic islet. Methods Solution of nidus vespae was extracted with ethanol from its herb. Rat lymphocyte and pig pancreatic islet were isolated and then were mixed together and cultured in incubators of 37 ℃ (concentration in volume: 5%CO2). Three different concentrations of extracted solution of nidus vespae （experimental group Ⅰ: 4.0 g/ml, group Ⅱ: 0.4 g/ml, group Ⅲ: 0.2 g/ml） were added to the mixed culture system of lymphocyte, respectively. Radioactive nuclide counts per minute were measured by 3H-thymdine test in order to examine the role of nidus vespae in inhibiting blatisation of lymphocyte, and the results were also compared with control group and CsA group, respectively. Results The counts were all reduced significantly (P＜0.001) in 3 experimental groups compared with control group (group Ⅰ 45.3%, group Ⅱ 29.6%and group Ⅲ 9.2%). It also showed that the inhibitory effect became ber in higher concentration but still weaker than that in CsA group (80.7%). Conclusion Nidus vespae could inhibit the blastisation of lymphocyte in mixed culture system of lymphocyte and pancreatic islet, and the effect increased as the the concentration increased, which may suggest that nidus vespae could suppress the rejection induced by T cells.
Objective To investigate the effect of interleukin-10 （IL-10） gene transfer on expression of CD44, selectin-E, lymphocyte function associated antigen-1 （LFA-1）, vascular cell adhesion molecule-1 （VCAM-1） in mice heart transplantation rejection. Methods Model of mice cervical heterotopic heart transplantation was set up, 96 mice were divided into three groups with random number table, control group： heart transplantation between C57 mice; transplant group： heart from BALB/C mice transplant to C57 mice; IL-10 group： IL-10 was transfected on BALB/C mice isolated heart for 1 hour, then transplanted to C57 mice. The messenger ribonucleic acid （mRNA） level expression of CD44 ,selectin-E ,LFA-1 ,VCAM-1 and IL-10 were measured by reverse transcription-polymerase chain reaction （RT-PCR） at the 5th day after transplantation. Results The mRNA level expression of CD44, selectin-E ,LFA-1 ,VCAM-1 in transplant group were significantly increased than those in control group （P〈0.01）. The mRNA level expression of CD44, selectin-E, LFA-1 ,VCAM-1 in IL-10 group were significantly decreased than those in transplant group （P〈0.01）. Conclusion IL-10 gene transfer is able to decrease the expression of CD44, selectin-E,LFA-1 ,VCAM-1 and suppress the heart transplantation rejection in mice.
Objective To investigate the inhibitory effect and its mechanisms of TLSFJM (JM acute T leukemia cell line derived suppressor factor) on allograf t rejection of small bowel t ransplantation in rat , and to compare the effect s and complications of TLSFJM with those of FK506. Methods One hundred male Brown Norway (BN) rats and 100 Lewis(L EW) rat s were t reated as donors and recipient s of small bowel t ransplantation , respectively. Then they were divided into five groups according to the dose of administ ration of TLSFJM and/ or FK506 : small bowel transplantation group (SBT group) ; large dose of FK506 〔0. 5 mg/ ( kg ·d) 〕group ; small dose of FK506 〔0. 25 mg/ (kg ·d) 〕group ; TLSFJM 〔10 U/ ( kg ·d) 〕group ; TL SFJM 〔10 U/ ( kg ·d) 〕associated with small dose of FK506 〔0. 25 mg/ (kg ·d) 〕group. FK506 and TLSFJM were administered through int ramuscular or int raperitoneal injection , respectively. Survival time , body weight , hepatic and renal function and histopathology of recipient s in each group were observed. Results TLSFJM took no damage effect on the recipient s’renal and hepatic functions 7 days after administ ration. When TLSFJM was administ rated associated with small dose of FK506 in small bowel transplantation , it could not only effectively suppress rejection reaction , extend recipient’s survival time , but also decreased the dosage of FK506 and prevented the side effect s. But TLSFJM may not be used as immunosuppressive agent alone for the prevention and treatment of rejection in rat small bowel t ransplantation because the rejection still existed. Conclusion As an effective immunosuppression agent , TLSFJM associated with small dose of FK506 can prolong the survival time of both recipients and graf ting small bowel , relieve intensity of rejection , and prevent the side effect s when high dosage FK506 is administ rated. TLSFJM may be used as a high-efficiency , low-toxicity immunosuppresive agent in small bowel transplantation.
Objective To summarize the clinical experience of liver retransplantation. Methods Six liver retransplantations were performed. The indications consisted of primary non-function (PNF, 2 cases), acute or chronic rejection (2 cases), stomas stenosis of biliary tract (1 case) and primary sclerosing cholangitis (1 case). The immunosuppressive protocols included tacrolimus, methylprednisolone (MP) and mycophenolate mofetil (MMF). Results Five patients were cured. One patient died on day 4 after liver retransplantation because of multiple organ failure. Postoperative complications included deep fungal infection and wound infection. Conclusions Liver retransplantation is an effective method for graft failure after liver transplantation. Proper indication and optimum operative time, intensive perioperative supervision and proper treatment are very important to improv effect of liver retransplantation.
Objective To introduce the research progress in the immune of composite tissue allotransplantation. Methods The related articles were reviewed to summarize the immune characteristics, experimental developments, and cl inical experiences of composite tissue allotransplantation. Results Composite allogeneic tissue is on the body surface, including the composition of the complex with high antigenicity. There are a lot of differences in the immune responsesbetween composite tissue allotransplantation and organ transplantation, such as immunosuppressant protocol, rejectiondiagnosis, and chronic rejection. Conclusion In the next study, it is urgently needed to learn these experiences and toestabl ish the special standard of composite tissue allotransplantation in induction of immune tolerance, local medication, and rejection diagnosis.