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Study Of Immunosuppressor Effects On Pretreated Donor In Canine Tracheal Allotransplantation

Posted on:2005-11-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2144360125450633Subject:Surgery
Abstract/Summary:PDF Full Text Request
Recipients must receive immunosuppressor to suppress the immune rejection over a long period of time after tracheal allotransplantation, but this will bring the recipients with the severe commplications. Now the best way is to induce the acceptor to build up immune tolerance for the transplant organ. If the tolerance that immunosuppressor bring can be successful, the construction and function of the transplant organ will keep normal, the recepient will survive with less injury.Materials And Methods:Twenty adult experimental dogs were used, four dogs were donor, the others were recepient. Donors group: four dogs were killed and all tracheas were divided into sixteen segments, eight segments pretreated by immunosuppressor were experimental group, the others were control group, the length of each segment was three centimitres.TheCTX(Cyclophosphamide 750mg) and MPED(Methylprednisolonum 2g) were injected to pretreated donor six hours before operation. Experimental groups of recipients: the sixteen dogs were randomly divided into two groups, each group was eight dogs. Group 1 (n=8) : the tracheal segments pretreated were wrapped with omentopexy in the recipient abdominal cavity. These dogs were not given immunosuppressor after operation. Group 2 (n=8): the eight normal tracheal segments were wrapped with omentopexy in the recipient abdominal cavity. These dogs were given immunosuppressor(Azathioprinum AZP 1.5mg.Kg.d , MPED 2mg. Kg. d) after operation.All recipient animals were killed after breeding for three weeks and the tracheal segments wrapped were taken out, the outcome of transplantation was evaluated by histological analysis according to scale of immune reaction.Results:Groups 1 (n=8): the normal histological construction was keeped in the seven tracheal segments and only with afew of scattered lymphocytes . The severe immune rejection was found in one segment. Groups 2 (n=S): three segments showed mild rejective reaction, the moderate rejection was found in the three segments , the severe rejection was found in the two tracheal segments.Conclusion:These findings demonstrate that pretreatment of donor can protect the function and construction of the allogeneic trachea, induce recipient immune tolerance. The mechanism may relate with function of the dendritic cell (DC). Mature DC can cause the imune rejection. The immature DC located in mucosa and parenchyma of the organs can secrete the IL-10, induce the TH2 type cell response and regulate the Tr-1(tregulator-l)cell to prevent the expression of co-stimulated molecules, break the balance of the .Thl/Th2 function and repress the synthesis of IL-12. Immature DC in donor can migrate into the recipient through lymphatic vessel, it will induce the establishment of stable allogenic chimerism, immature DC also can induce formation of immune tolerance. The study of tracheal antigen showsthat tracheal mucosa contains the strong antigenicity , cartilage cell and perichondrium contain the mild antigenicity .According to the DC origin and distribution the immature DC primarily locates in the submucosal tissue and mucosa of trachea. Before the blood-supply formation in trachea after allotransplantation, tracheal mucosa will gradually necrosise ,which will severely stimulate immature DC and make DC catch the cell fragments to incline mature and activation .After lymphatic vessel connecting donor and recipient was rebuilt, the mature DC will migrate into recipient lymh node and spleen ,present antigen to T-cell, induce immune reaction by direct routes toward sensitization. After transplanted trachea was rebuilt with the blood circulation, the DC in recipent will enter trachea and induce immune reaction by indirect routes toward sensitization. In this study, the donors were given the AZP and MPED six hours before operation, which will suppressed immature DC to become mature and imterrupt the direct routes toward sensitization. After the blood-supply connecting donor and recipient was formed, the immature DCof donor will migrate into the lymph node and spl...
Keywords/Search Tags:tracheal transplantation, immunosuppression, immune tolerance
PDF Full Text Request
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