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The Immunosuppressive Effects Of Tacrolimus And Ulinastatin In Rat Small Bowel Transplantation

Posted on:2006-11-08Degree:MasterType:Thesis
Country:ChinaCandidate:X M ChenFull Text:PDF
GTID:2144360152993225Subject:Immunology
Abstract/Summary:PDF Full Text Request
Small bowel transplantation(SBT) is the radical way of therapy for patients with intestinal failure and congenital abnonnality. Dettering had been implied SBT in clinic since 1964, but not successful due to serious rejection. Because intestine and its mesentery contain large amount lymph tissues, and because of slow recovery of intestinal function, bacterial translocation and serious infection, Small bowel becomes the most serious organ that occurs rejection and has the highest incidence of rejection in organ transplantation. So the development of human SBT is very slow in clinic. For human being, there are still three ticklers-serious rejection, recovery of function, and infection after SBT that have not been improved in essence, although application of Cyclosporine A (CsA) has greatly improved the experimental results of SBT, and the rats can survive for long-term after transplantation under the treatment of immunosuppressant-tacrolimus(FK506). Intestinal transplantation has evolved from an experimental procedure to one of the standard therapy measures for patients with intestinal failure through endeavors for several decades , which with gradually advancing technique and with greatly improving the survival rate of recipients.FK506 is a novel efficient immunosuppressant, and its effect of immunosuppression has manifested by animal experiments and clinical organ transplantations since it was applied in early 1990s. FK506 suppress the generation of interleukin-2 via block the signal passageway of its transcription that calcium dependent, and then inhibit the immuno-response of T lymphocyte. But the adverse effects (nephrotoxicity, neurotoxicity, and hyperglycemia) of tacrolimus will become increasing company with the dose upwards. People usually adopt combination with an another immunosuppressant in order to reduce its adverse effects as to abtain the same efficiency, and have achieved some success. As a protease inhibitor, it is reported that ulinastatin (UTI) can suppress sorts of proteases ,stabilize lysosomal membranes, clear up oxygen free radicals (OFRs), and can inhibit expression of inflammatory cytokines. It has been used in treatmentof acute pancreatitis, protect against shock and operation. It is used in organ transplantation too. Presently, it is found that UTI possesses suppressive effects to some inflammatory cytokines (interleukin-2, interleukin-8, etc), and can protect kidney function via suppresses several proteases. So there are great prospective applications with UTI.We successfully established the stable heterotopic segment intestinal transplantation in rat by endeavors for several months, and have carried out a series of studies on base of the models. First, we divided recipients into 6 groups in random. In these 6 groups, FK506 and UTI are applied respectively or together so as to observe the immunosuppressive effects of FK506 and UTI in rat SBT through contrasting recipients survival and pathology of grafts after operation. In result, pathologic slices showed that rejections of grafts(donor intestine) in FK506 group and FK506+UTI group were significantly milder than that in the other groups. In survival, there were very significant differences between FK506 group, FK506+UTI group and control group, UTI group(p<0.01); Significant differences also existed between 1/2FK506 group, 1/2FK506+UTI group and control group(p<0.05), in which it showed very significant differences between 1/2FK506+UTI group and control group (p<0.01); In addition, differences between FK506 group, FK506+UTI group andl/2FK506 group showed significantly, and in which it showed very significant differences between FK506+UTI group and 1/2FK506 group (p<0.01); Whereas there was no difference among FK506 group, FK506+UTI group and 1/2FK506+UTI group (P>0.05); And had no difference between control group and UTI group.In every organ transplantation, the graft will be confronted to a procedure of ischemia-reperfusion(I/R) inevitably, and will be injured in a certain degree during this procedure. Because of its unique characteristic...
Keywords/Search Tags:tacrolimus, ulinastatin, small bowel transplantation, immunosuppression ischemia-reperfusion injury
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