denoviral cardiotrophin-1 transfer improves survivaland early graft function after ischemia and reperfusionin rat small-for-size liver transplantation model

his study was to investigate the effect of donor liver adenoviral cardiotrophin-1(CT-1) gene transfer on early graft survival and function in rat small-for-size livertransplantation. We constructed a recombinant murine CT-1 adenoviral vector.Donor rats were transduced in vivo with adenoviruses expressing CT-1 (AdCT-1)or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40%of weight, and transplanted. A syngeneic rat orthotopic liver transplantationmodel was performed using 40% small-for-size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cellsurvival signaling pathways were assessed. AdCT-1 pretreatment markedlyimproved liver function and the survival of small-for-size grafts. In the CT-1treatment group, hepatic architecture was well protected, apoptotic and necroticcells were reduced; anti-apoptotic protein bcl-2 was up-regulated and proapoptotic cleaved caspase-3 was down-regulated, cell survival signaling pathwayswere activated by phosphorylation of protein kinase B (Akt), extracellular-regulated kinase (ERK) and Signal transducer and activator of transcription-3 (Stat-3) after transplantation. In conclusion, donor liver adenoviral CT-1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosisin small-for-size liver transplantation, mediated in part by activation of the Akt,ERK, and Stat-3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small-for-size liver grafts.