FK506 combined with GM6001 prevents tracheal obliteration in a mouse model of heterotopic tracheal transplantation

Abstract Background Obliterative bronchiolitis (OB) is the major complication limiting the long-term survival of allografts after lung transplantation. In this study, we investigated the effect of tacrolimus (FK506) combined with GM6001，a matrix metalloproteinase (MMP) inhibitor， on the formation of OB using a mouse heterotopic tracheal transplantation model. Methods Syngeneic tracheal grafts were transplanted heterotopically from BALB/c mice to BALB/c mice. Allografts from C57BL/6 mice were transplanted to BALB/c mice. Isograft group, allograft group, allograft+FK506 group, allograft +GM6001 group and allograft+FK506 + GM6001 group was given respectively intraperitoneal injection of saline, saline, FK506, GM6001 and FK506 + GM6001 once a day. At 28 day after transplantation, OB incidence was determined by hematoxylin-eosin staining and the expressions of MMPs and cytokines were assessed using enzyme linked immunosorbent assay, immunohistochemical assays and western blot assay. Results The tracheal occlusion rates of isograft group, allograft group, allograft+FK506 group, allograft+GM6001 group and allograft+FK506 + GM6001 group were 0, 74.1 ± 9.79%, 34.4 ± 6.04%, 40.3 ± 8.77% and 26.5 ± 5.73% respectively. There were significant differences between the latter two groups (P  Conclusion FK506 combined with GM6001 could alleviate tracheal obliteration in mouse heterotopic tracheal transplantation model, due to its inhibitory effect on MMPs.