The Effect Of HO-1 Gene Transfection On Bronchiolitis Obliterans After Lung Transplantation In Rats

OBJECTIVE To establish the rat orthotopic tracheal transplantation model to simulate allogeneic lung transplantation associated with bronchiolitis obliterans(OB).Compare treatment effect of OB between the heme oxygenase-1 gene(HO-1)group and the cyclosporine(CsA)group.METHODS Orthotopic tracheal transplantations were performed in allogeneic(Wistar-SD)and syngeneic(SD-SD)models.Physiological saline(NS),CsA,adeno-associated virus mediated rat heme oxygenase-1 gene(AAV-rHO-1)was used for intervention models(Wistar-SD)respectively.Grafts were harvested after 7,30 and 60 days post-transplant for histologic evaluation.Compare the transversal surface,CD4 + and CD8 + T lymphocytes in peripheral blood,and Apoptotic Index between different intervention models.RESULTS 1.Compared with SD-SD models,transversal surface was smaller in NS intervention models(P<0.01).2.Compared with CsA intervention models,there were less infiltration of chronic inflammatory cells,interstitial edema,interstitial fibrosis in AAV-rHO-1gene intervention models.3.Compared with CsA intervention models,there were less CD4 + and CD8 + T lymphocytes in peripheral blood in AAV-rHO-1gene intervention models.4.Compared with CsA intervention models,there were less apoptosis of trachea transplantations.CONCLUSIONS The pathophysiological changes of rat orthotopic tracheal transplantation model are very similar to the OB of human lung transplantation.HO-1 gene can significantly reduce the infiltration of chronic inflammatory cells,interstitial edema,interstitial fibrosis,and protect epithelial cells.These results suggest that HO-1 may be a new option for OB gene therapy in lung transplantation.