摘要
AIM: To study the mechanism and effect of nuclear factor-κB (NF-κB) activation and inflammatory response on the extended cold-preserved graft injury after orthotopic liver transplantation (OLT). METHODS: OLT was performed in rats with varying time of cold ischemia grafts (6, 18 and 24 h in University Wisconsin solution at 4 ℃). We determined the time of NF-κB activation and expression of tumor necrosis factor-α (TNF-α), cytokineinducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) within 6 h after reperfusion. Serum alarming aminotransferase (ALT), neutrophil sequestration, circulating neutrophil CD11b and L- selectin expression were also evaluated. RESULTS: The accumulation of neutrophils in the graft was significantly increased in the 18 h and 24 h cold-ischemia groups within 0.5 h after reperfusion, compared with the 6 h group. But the strongly activated neutrophils was slightly increased at 2 h after reperfusion and remained at high levels 4 h after reperfusion, which was synchronized with the common situation of recipients after transplantation. Prolonged cold-preservation did not affect neutrophil accumulation and activation. NF-κB activation preceded the expression of TNF-α, CINC, and ICAM-1 in the liver, which was significantly increased with prolonged cold preservation. In prolonged cold preserved grafts, prominently elevated NF-κB activation occurred at 0.5 h and 1 h, compared with that at 2 h after reperfusion, which was consistent with greatly increased intrahepatic TNF-α response. CONCLUSION: NF-κB activation is correlated with the expression of TNF-α, CINC, and ICAM-1 in vivo in OLT rats. Extended cold preservation of grafts might up-regulate TNF-α, CINC, and ICAM-1 expression in the grafts, most probably through elevated NF-κB activation, and might contribute to neutrophil infiltration in the grafts after reperfusion. Elevated NF-κB activity is harmful to inflammatory response in the grafts, and inhibited NF-κB activity might protect against early graft injury after liver transplantation.
AIM:To study the mechanism and effect of nuclear factor- κB (NF-κB) activation and inflammatory response on the extended cold-preserved graft injury after orthotopic liver transplantation (OLT). METHODS:OLT was performed in rats with varying time of cold ischemia grafts (6,18 and 24 h in University Wisconsin solution at 4℃).We determined the time of NF-κB activation and expression of tumor necrosis factor-α (TNF-α),cytokine- inducible neutrophil chemoattractant (CINC),and intercellular adhesion molecule-1 (ICAM-1) within 6 h after reperfusion. Serum alarming aminotransferase (ALT),neutrophil sequestration,circulating neutrophil CD11b and L- selectin expression were also evaluated. RESULTS:The accumulation of neutrophils in the graft was significantly increased in the 18 h and 24 h cold-ischemia groups within 0.5 h after reperfusion,compared with the 6 h group.But the strongly activated neutrophils was slightly increased at 2 h after reperfusion and remained at high levels 4 h after reperfusion,which was synchronized with the common situation of recipients after transplantation. Prolonged cold-preservation did not affect neutrophil accumulation and activation.NF-κB activation preceded the expression of TNF-α,CINC,and ICAM-1 in the liver,which was significantly increased with prolonged cold preservation. In prolonged cold preserved grafts,prominently elevated NF-κB activation occurred at 0.5 h and 1 h,compared with that at 2 h after reperfusion,which was consistent with greatly increased intrahepatic TNF-α response. CONCLUSION:NF-κB activation is correlated with the expression of TNF-α,CINC,and ICAM-1 in vivo in OLT rats. Extended cold preservation of grafts might up-regulate TNF-α, CINC,and ICAM-1 expression in the grafts,most probably through elevated NF-κB activation,and might contribute to neutrophil infiltration in the grafts after reperfusion.Elevated NF-κB activity is harmful to inflammatory response in the grafts,and inhibited NF-κB activity might protect against early graft injury after liver transplantation.
基金
Supported by the Education Foundation of Xuzhou Anesthesia Laboratory,Jiangsu,No.KJS02055
