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The Experimental Research On Combined Liver/Small Bowel Transplantation In Rats

Posted on:2003-09-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:N LuFull Text:PDF
GTID:1104360062995194Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
In order to explore the immunological interaction and its features in combined organs transplantation, a rat model of en bloc liver/small bowel transplantation (LSBTx) was developed by microsurgical procedure, in which Wistar and SD were dedicated as donor and recipient respectively. The technical focus of model establishment was studied and summarized. The survivals of donors and grafts were observed and compared with that in isolated liver or small bowel transplantation groups.Samples of graft were harvested on POD5, 7 and 14 for sequential histological examination. Intragraft apoptosis was tested by TUNEL method. Semiquantitative PCR was adopted to analyze intragraft expression of perforin and granzyme B coding genes. Fas and Fas-L expression were detected by immunohistological assay. A pilot research on the effect of multiglucoside tripteygii (Tn) treatment on liver/small bowel transplantation was carried out also.To establish a stable model, 103 antecedent trials were performed. The final successful rate of LSBTx was 63.15% with over 70% recipients survived more than 28 days companied by all recipients survival in isolated LTx group in same duration. In contrast all recipients in SBTx died within 20 days due to allograft rejection. The histological examinations demonstrated that a typical "reject-type" infiltration as a clear sign of cellular rejection in all three groups, particularly in the periportal area of the liver graft and in the crypts of the transplanted intestine. In the intestinal graft, the infiltrate expanded within 1 week , in SBTx group it progressed until the graft was completely rejected, while in the LSBTx group the mucosal epithelium had recovered with regular distribution of goblet cells on POD 14, comparing the appearance during the rejection episode on POD7. The maximum number of infiltrating cells in the liver graft was found 14 days after the operation. The maximum number of apoptotic cells was found on POD7 in intestinal graft, which was much less in the LSBTx group than in the SBTx, and regressed on POD 14 in LSBTx comparing that on POD7. The maximum apoptosis of parenchymal cells in-3-liver graft was observed on POD7, which was prior to the fully developed infiltration in the periportal area that was accomplished 1 week after operation. PCR showed that the level of expressions of perform and granzyme B in the intestinal graft in the LSBTx group was lower than that in the SBTx, meanwhile immunohistological staining found that the level of expression of FasL was in a reverse pattern. Expressions of FasL in liver graft was getting more intense from POD7 to POD 14. The number of graft infiltrate cells (GIC) and the expressions of peforin and granzyme B had been getting less following the treatment of TU after combined liver/small bowel transplantation. As a conclusion: (1) The model of en bloc liver/small bowel transplantation in rat is able to be established stably, skillful microsurgical performance and proper peri-operative treatment are essential to achieve success in model establishment; (2) The model is very suitable to develop pre-clinical research because of its close relation to the transplantation technique in humans; (3) It is an ideal model to investigate the special phenomena after liver/small bowel transplantation on account of its advantages that both graft are from the same donor and are transplanted simultaneously, the liver graft is arterialized and the intestinal graft is drained via the portal vein into the transplanted liver; (4) In the strain combination of Wistart to SD, the allo graft of simultaneously transplanted liver and small bowel can be accepted spontaneously; (5) The initial phase after liver/small bowel transplantation is associated with activation of lymphatic system, which implies that the mechanism of acceptance induction is an active process; (6) The severity of rejection has a compact on apoptosis of intragraft parenchymal cells; (7)The expressions of perform and granzyme B can serve as indictors of activation of cytotoxic T lympho...
Keywords/Search Tags:Transplantation
PDF Full Text Request
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