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.
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 insure early detection and hence efficient prevention of allograft rejection in transplanted heart, investigate possible applications of NAD(P)H fluorescence components analysis at the level of living cardiac cells to propose new approaches for diagnosis of rejection. Methods NAD(P)H was studied for noninvasive fluorescent probing of the mitochondrial function. Human cardiomyocyte were isolated from one additional endomyocardial biopsy (EMB) of 14 pediatric patients with heart ransplantation. Rat cardiomyocyte (n=5, 13-14 week old) were also isolated by the same approach for human myocytes. Autofluorescence(AF) was recorded in living cardiomyocytes following excitation with 375 nm UVlight and detection by spectrallyresolved time correlated single photon counting (TCSPC), based on the simultaneous measurement of the fluorescence spectra and lifetimes. Rat cardiac cells were divided into four groups: normoxic condition, normoxia with Rotenone, ischemic condition and ischemia with Rotenone. Comparison of cardiomyocyte AF between human and rat; compared kinetics of rat cardiomyocytes AF in normoxic conditions to ischemiamimicking ones, induced at physiological temperatures by reducing cell pH and oxygen content; comparison of cardiomyocyte AF dynamic changes in transplanted pediatric patients presenting either no rejection (R0) or mild rejection (R1). Results We have achieved appropriate isolation of living cardiomyocytes from human biopsies, as well as from rat cardiac tissues and determined their AF. At least a 3-exponential decay with 0.5-0.7ns, 1.9-2.4 ns and 9.0-15.0 ns lifetime pools is necessary to describe human cardiomyocyte AF within 420560 nm spectral range. Rat cardiomyocyte steadystate AF in ischemiamimicking condition was significantly increased when compared normoxic ones (Plt;0.05); application of Rotenone induced a significant increase in AF intensity in ischemic and normoxic condition, however no significant difference between the two groups (Plt;0.05).Human cardiomyocyte AF was found significantly lower in comparison to experimental rat model in the same condition(Plt;0.05). A correlation between changes in steadystate NAD(P)H fluorescence and rejection grades was found when comparison of R1 to R0. R1 showed significantly increased fluorescence intensity (Plt;0.05), without change in the spectra shape, results can be comparable to the effect of ischemiamimic conditions. Conclusion Our studies clearly demonstrated that spectrallyresolved fluorescence spectral analysis coupled to fluorescence lifetime are high sensitive approaches to examine mitochondrial metabolic oxidative state directly in living human cardiomyocytes with good reproducibility. Human cardiomyocytes are more metabolically active than the rat ones, while this activity (and thus ATP production) seems lowered during rejection process. In perspective, the advantage of this method is the possibility of its combination to multiphoton confocal microscopy, which can result in the adaptation of this approach directly to tissue biopsy, as well as in vivo directly via cardiac catheterization without the necessity of cell isolation. This approach provides promising new tool for clinical diagnosis and treatment of allograft rejection, and will enhance our knowledge about cardiomyocyte oxidative metabolism and/or its dysfunction at a cellular level.
ObjectiveTo compare tacrolumus (FK506) with cyclosporine A (CsA) in clinical application to organ transplantation.MethodsThe literature in recent years has been reviewed and compared. ResultsFK506 was a powerful immunosuppression with a mechanism of action similar to that of CsA, but significantly superiori to CsA in terms of prophylaxis and treatment of allograft acute rejection, delay of chronic rejection, and withdrawal of steroid in early period. The cardiovascular mortality and chronic graft nephropathy (CGN),such as hypertension and hyperlipidemia were less frequently seen in FK506treated patients and FK506 also had an acceptable safety profile, including a low incidence of hypertrichosis,gingival hyperplasia and infections.However, CsA had been showed a better result in prevention of posttransplantation diabetes mellitus (PTDM ) and more economic agent than FK506. Pharmacokinetic studies showed CsA in the form of Sandimmun Neoral showed less inter an intrapatient variability than FK506.Meanwhile, the combination of MMF and FK506 or CsA has been proved effectively with excellent graft and patients survival. Conclusion FK506 and CsA are safe and effective long term maintenance immunosuppressive agents in organ transplantation with wonderful prospect.
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.
ObjectiveTo reporte the nursing experience of non-healing incision due to allograft rejection after osteosarcoma surgery. MethodsOne patient with non-healing incision due to allograft rejection after osteosarcoma surgery treated in September 2013 was selected. The suitable moist healing dressings was chosen to control inflammation, prevent infection, manage exudation, promote the growth of granulation, protect the surrounding skin, shorten the dressing time and reduce the suffering of patients. ResultThe wound healed well after 65 days of dressing with the function of the right upper limb recovered. ConclusionThe moist healing dressing not only improved the quality of patient's life and increased the patient's confidence of overcoming the disease, but also made the patients more active to cooperate in the next treatment.
Objective To investigate the expression of RNA editase ADAR1 in the lymphocytes in rats’ spleen with liver transplantation rejection. Methods Thirty SD rats and 75 Wistar rats were included. Fifteen livers from Wistar rats were transplanted to 15 Wistar rats (isograft group), 30 livers from SD rats were transplanted to 30 Wistar rats (allograft group and allograft+FK506 group), and 15 of them were then intramuscularly injected with FK506, 2 mg/(kg·d), the other 15 Wistar rats were only operated similarly to the other rats without any liver transplantation (control group). Five rats were killed and their splenetic tissues were collected on day 3, day 5, and day 7, respectively. The expression of ADAR1 mRNA in lymphocytes of the spleen in acute rejection was detected by RT-PCR. Results Different performance of pathology was observed in all the liver and spleen tissues from the transplanted rats over time, especially in allograft group. The expression of ADAR1 mRNA in the allograft group was significant higher than that of isograft and allograft+FK506 groups （P＜0.001）, especially on the 5th day. Conclusion There was a significant positive correlation between expression of ADAR1 and the severity of acute rejection, but the mechanism by which ADAR1 affected the acute rejection is unknown and needs to be further studied. FK506 may inhibit the expression of ADAR1 and remarkably reduce the severity of acute 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.
【Abstract】ObjectiveTo explore the effects of p38 mitogenactivated protein kinase (MAPK) on apoptosis of small intestinal epithelial cells after transplantation in rats. MethodsSmall intestinal transplantation was performed in SD and Wistar rats. The recipients were divided into three groups: isograft group (Wistar→Wistar group), allograft group (SD→Wistar group) and allograft+cyclosporine A group (SD→Wistar+CsA group). The grafts were harvested on day 1, 3, 5 and 7 after operation. All graft samples were subjected to histological examination. The apoptosis of graft epithelial cells was detected by TUNEL method. p38 MAPK was measured by Westernblotting method and serum TNFα was determined by ELISA. ResultsMild, moderate and severe rejection reaction occurred in the SD→Wistar group, it was showed that the number of apoptotic cells increased with the severity of the rejection reaction by TUNEL. In SD→Wistar group, the numbers of apoptotic cells were significantly higher than those of the other two groups （P＜0.01）. The severity of rejection reaction in SD→Wistar+CsA group was less than that of SD→Wistar group and the number of apoptotic cells increased with the severity of the rejection reaction (P＜0.01). The level of serum TNFα varied with the apoptotic degree of small intestinal epithelial cells in SD→Wistar group and SD→Wistar+CsA group （P＜0.01）. The expression of p38 MAPK increased with the number of the apoptotic cells in SD→Wistar group and SD→Wistar+CsA group （P＜0.01）, but there was no evident change in Wistar→Wistar group （Pgt;0.05）. The expression of p38 MAPK and the level of serum TNFα were positively correlated with apoptosis in small intestinal rejection after transplantation （r=0.875， P＜0.01； r=0.837， P＜0.01）. p38 MAPK and TNFα were also positively correlated （r=0.826，P＜0.01）. ConclusionApoptosis plays an important role in small intestinal rejection. p38 MAPK is involved in apoptosis and is an important regulator in signal pathway of cell apoptosis.
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.