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 per...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.展开更多
NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control th...NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.展开更多
基金Supported by the Education Foundation of Xuzhou Anesthesia Laboratory,Jiangsu,No.KJS02055
文摘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.
基金National Natural Science Foundation of China （No. 30571909） the Youth Teacher＇s Research Foundation of Jiangsu Province, China （No. BU 134701 ） the Medical Development Foundation of Soochow University （No. EE134615）.
文摘NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.
