Simvasatin plus cyclosporin A inhibits obliterative bronchiolitis in a murine heterotopic tracheal transplant model / 中华器官移植杂志

ABSTRACT

Objective To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model .Methods Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients .Transplanted animals received either control chow ,chow containing simvastatin ,chow containing cyclosporine A ,or chow containing simvastatin and cyclosporine A . beginning immediately after transplantation .Epithelial loss and luminal obstruction were analyzed by morphometry .Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts .collagen deposition was studied by picro sirius red staining .Group t test was used to calculate the difference between groups .Results simvastatin combined with cyclosporin A treatment reduced chemokine (MCP-1 , RANTES ) release , inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts ,resulting in limited bronchial inflammation and diminished epithelial loss .simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells ,reduced M M P-2 release and decreased the amounts of type I and III collagen deposition ,resulting in preserved luminal patency and inhibited development of OB compared with those of controls .Conclusions When simvastatin was used in combination with CsA ,the development of OB was significantly inhibited .