Suppression of Nuclear Factor-κB Activity in Kupffer Cells Protects Rat Liver Graft From Ischemia-Reperfusion Injury

Objective. The objective of this study was to investigate the protective effect and mechanisms of nuclear factor (NF)-kappa B decoy oligodeoxynucleotides (ODN) on rat liver grafts following ischemia-reperfusion injury (IRI). Methods. Animals were randomly divided into 3 groups (n = 8): control ischemia-reperfusion (IR) and decoy ODN groups; in the last cohort donor grafts were transfected with 120 mu g NF-kappa B decoy ODN before procurement. Following 2 hours of reperfusion, NF-kappa B binding activity was detected in isolated Kupffer cells (KCs) using electrophoretic mobility shift assays (EMSA). Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 messenger RNA (mRNA) expressions were analyzed using reverse transcriptase polymerase chain reaction (RT-PCR) methods. Liver tissue and blood serum were collected for histopathologic examination and liver function test, respectively. Results. The NF-kappa B binding activity, TNF-alpha and IL-6 mRNA expression as well as serum ALT and total bilirubin levels were significantly increased compared with the control group following reperfusion (P < .01). A large number of hepatocytes showed degeneration and necrosis. However, these indices were significantly ameliorated among the decoy ODN group (P < .01) with preserved hepatic lobule architecture. Conclusion. KCs NF-kappa B activation following reperfusion plays an important role in IRI after liver transplantation. The decoy strategy showed an apparent effect to suppress NF-kappa B activation and inhibit production of downstream cytokines, thereby protecting liver grafts from IRI.