Transfection of nuclear factor‐kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model

Abstract

Nuclear factor-kappaB (NF-κB) is considered to play an important role in the response to ischemia/reperfusion (I/R) injury in flap surgery. To inhibit NF-κB, synthetic double-stranded oligodeoxynucleotide (ODN) was used as a decoy. The present study aimed to evaluate the suppressive effects of NF-κB against I/R injury of experimental rat flap model. An extended epigastric island flap was raised and ischemia was induced for 3 h. NF-κB decoy ODN (group D) or single-strand ODN (control; group S) was injected via the contralateral artery when the pedicle was clamped. Transfection efficiency was evaluated with fluorescein isothiocyanate (FITC)-labeled ODN. The effects of NF-κB decoy ODN were analyzed in groups D and S, and an untreated group (group N). FITC-labeled ODN was distributed over the entire flap. Mean survival rate of the flap was significantly higher in group D than in the other groups (group D: 57.9%; group S: 31.1%; group N 31.7%; p < 0.005). Injured muscle fibers, neutrophils and the expression of inducible nitric oxide synthase were significantly lower in group D. A real-time polymerase chain reaction also demonstrated a tendency for suppression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6. We show that NF-κB decoy ODN protected against flap necrosis as a result of I/R injury in rats. We also indicate that intra-arterial injection of naked NF-κB decoy ODN is effective for transfection into target organs. Therefore, transfection of NF-κB decoy ODN represents a novel therapeutic strategy for the treatment of flap surgery in I/R injury.