Role of NF-κB as Effector of IPC in Donor Livers Before Liver Transplantation in Rats

Abstract

The objective of this study was to investigate the effect of ischemic preconditioning (IPC) on NF-κB activity during reperfusion early after liver transplantation in rats. Methods Male Sprague-Dawley (SD) rats were used as donors and recipients of orthotopic liver transplantations. The donor liver was stored 2 hours in Ringer’s solution at 4°C preimplantation. IPC was performed by clamping of the portal vein and hepatic artery of the donor for 10 minutes followed by reperfusion for 10 minutes before harvesting. At 1, 2, 4, and 6 hours after portal vein reperfusion, graft samples were obtained to determine hepatic levels of NF-κB activity, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1. Blood samples were obtained to measure serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Results After liver transplantation without IPC, serum levels of ALT and LDH increased significantly compared with the sham-operated group. Among the IPC group, serum ALT and LDH decreased significantly. NF-κB activity in the graft increased within 6 hours after transplantation. Among the IPC group, NF-κB activity was significantly attenuated. Hepatic levels of TNF-α and ICAM-1 were significantly elevated in the non-IP group but both were reduced in the IPC group. Conclusion IPC downregulated TNF-α and ICAM-1 expression in the graft, most likely through decreased NF-κB activation, and attenuated neutrophil infiltration after reperfusion.