Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion

摘要: Abstract Background Sphingosine-1-phosphate regulates endothelial barrier integrity and promotes cell survival proliferation. We hypothesized that upregulation of sphingosine-1-phosphate during ex vivo lung perfusion would attenuate acute injury improve graft function. Methods C57BL/6 mice (n = 4-8/group) were euthanized, followed by 1 hour warm ischemia cold preservation in a model donation after cardiac death. Subsequently, underwent with 1 4 different solutions: Steen solution (Steen, control arm), added (Steen + sphingosine-1-phosphate), plus selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or both additives (Steen + sphingosine-1-phosphate + sphingosine inhibitor). During perfusion, compliance pulmonary artery pressure continuously measured. Pulmonary vascular permeability was assessed injection Evans Blue dye. Results The combination ischemia, created significant compared lungs immediately harvested circulatory death put on perfusion. Addition alone did not significantly function without additives. However, group + resulted increased (110% ± 13.9% vs 57.7% ± 6.6%, P  0001) decreased (33.1 ± 11.9 μg/g 75.8 ± 11.4 μg/g tissue, P  = .04) alone. Conclusions Targeted drug therapy sphingosine-1-phosphate + sphingosine improves murine model. Elevation circulating via specific pharmacologic modalities may provide protection marginal donor leading to successful rehabilitation for transplantation.