Font Size: a A A

MiR-126-3p Regulation Of IRS1 Associated T Cells Glucose Metabolism Intervention Immune Tolerance After Mice Liver Transplantation

Posted on:2017-11-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:J C WangFull Text:PDF
GTID:1314330548954813Subject:Surgery
Abstract/Summary:PDF Full Text Request
Part ?:The relationship between glucose metabolism and tolerance in mice liver transplantation[Objectives]Allogeneic mouse has been liver transplantation will have a long-term survival without the need for immunosuppression,it is called Spontaneous immune tolerance.It maybe has the relationship with inhibition of T-cell function,and The function of T cells is closely related to their metabolism.The purpose of the experiment is to find out the relationship of the glucose metabolism of T cells and the formation of immune tolerance between syngeneic and allogeneic mouse.[Methods]mLT was used in this study for in-vivo study.Respectively,in vitro and in vivo studies in mice after liver transplantation has found the relationship between glucose metabolism and immune tolerance in liver transplantation.[Results]A significantly increasing the number of allogeneic T cells in mice liver after liver transplant.In the early liver transplantation(less than 4 weeks),allogeneic liver transplant has a large number of lymphocytes in the liver,liver tissue in varying degrees of damage;liver transplantation tolerance period(8 weeks),liver infiltrating lymphocytes decreased,regeneration,lobular structure back to normal.We found the liver glucose metabolism of allogeneic mouse after liver transplantation is stronger than the syngeneic by PET/CT.In vitro sorting the non-parenchymal cells of transplanted liver,and we found that glucose metabolism of CD4+T cells in allogeneic issignificantly stronger than the control group by ImmuKnow Kit.And we found miR-126-3p involved in glucose metabolism then influence the formation of immune tolerance of liver transplantation.[Conclusions]After mouse allogeneic liver transplantation,liver existence of a formation process of immune tolerance.T cells play an important role in the regulation of metabolic liver transplantation immune tolerance during.IRS1 by responding T cells may play an important role in the metabolism of liver transplantation tolerance in mice spontaneouslyPart ?:MiR-126-3p regulation of IRS1 associated T cells glucose metabolism intervention immune tolerance after mice livertransplantation[Objectives]Spontaneous immune tolerance of mouse liver transplantation has been one of the hotspot in transplantation immunology,The results of the first part of the description of the process of liver transplantation tolerance induction in mouse T cell glucose metabolism increased and decreased,and increased T cell has a synergistic relationship.By analyzing Mirna chip we found differential expression of miR-126-3P.These results prompt us:T cells play an important role in glucose metabolism in liver transplantation tolerance process.[Methods]Construction of allogeneic liver transplantation model.In the experimental group mice injected lentivirus transfected with siRNA inhibitor inhibits miR-126-3P.Then liver function,biopsy and survival rates were observed,and at different points in time separated and purified liver T cells,measured T cells glucose metabolism by ImmuKnow assay.[Results]After the injection of lentiviral siRNA inhibitors inhibit miR-126-3p expression in mouse liver,we found the expressin of IRS1(Insulin receptor substrate 1)in allogeneic mice liver non-parenchymal cells was significantly enhanced.Significantly lower survival rate and serum liver function increased significantly in the experimental group of mice than the control group.Histology showed a significant increase T cell infiltration in the transplant liver in experimental group,means rejection in.Meanwhile we found the metabolism of CD4+T cells reduced significantly in experimental group by ImmuKnow Kit.[Conclusions]miR-126-3p can negatively regulate the expression of IRS1,By enhancing the expression of IRS1 to enhance mouse liver T-cell glucose metabolism,thereby to interfere with the formation of immune tolerance in mice spontaneously.Thereby intervention the forming of mouse immune tolerance.
Keywords/Search Tags:Liver transplantation, T cells, glucose metabolism, miRNA chip, miR-126-3P, IRS1, T cell, siRNA
PDF Full Text Request
Related items