Fibronectin splice variant connecting segment-1 peptides protect sinusoidal endothelial cells and alleviate ischemia/reperfusion injury in rats / 中华器官移植杂志

ABSTRACT

Objective To examine the effect of fibronectin connecting segment-1 (CS1) peptidefacilitated blockade of inflammatory cells-fibronectin adhesion on a rat liver transplantation model of prolonged ex vivo cold ischemia.Methods A model of liver transplantation in Wistar→Wistar rat was established.The donors of the CS1 treatment group received CS1 peptides through the tail vein for 3 days before operation.Another two doses of CS1 peptides were administered into the liver intraportally during procurement and before transplantion.Recipients received an additional 3-day course of CS1 peptides after transplantation.Rats in control group received scrambled peptides.Rats were sacrificed at 6,24 and 72 h after transplantion,and plasma transaminase activity and hepatic pathological changes were studied.The inflammatory cells and liver sinusoidal endothelial cells were visualized histochemically.Real-time PCR was used to detect tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF) mRNA expression in the liver.Results The plasma transaminase activity and hepatic necrosis areas in CS1 treatment group were significantly lower than in control group (P＜0.05).CS1 peptides treatment significantly decreased the number of Kupffer cells after transplantation and greatly inhibited the recruitment of neutrophils to the graft liver as compared with control group (P＜0.05).After prolonged cold ischemia,only a few hepatic endothelial cells exhibited positive staining of hepatic sinusoidal endothelial cell biomarker SE-1.Lots of hepatic sinusoidal endothelial cells positive for SE-1 staining could be detected in CS1 group at 72 h after transplantation,while much less SE-1 positive cells presented in the control goup.Prolonged cold ischemia caused a significant increase of TNF-α,IL-1β and VEGF mRNA expression in the graft liver of control group after transplantation.The expression of TNF-α mRNA at 6 and 24 h and VEGF mRNA expression at 24 h were significantly lower in CS1 group than in control group (P＜0.05).Conclusion Peptide-mediated blockade of inflammatory cells-fibronectin interaction decreased the mRNA expression of inflammatory cytokines,prevented hepatic sinusoidal endothelial cells from injury and subsequently protected against severe ischemia/reperfusion injury of the graft liver after transplantation.