Transfection of nuclear factor-kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model
Version of Record online: 22 NOV 2012
Copyright © 2012 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 14, Issue 11, pages 623–631, November 2012
How to Cite
Uemura, T., Tsujii, M., Akeda, K., Iino, T., Satonaka, H., Hasegawa, M. and Sudo, A. (2012), Transfection of nuclear factor-kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model. J. Gene Med., 14: 623–631. doi: 10.1002/jgm.2677
- Issue online: 22 NOV 2012
- Version of Record online: 22 NOV 2012
- Accepted manuscript online: 19 OCT 2012 01:59AM EST
- Manuscript Accepted: 16 OCT 2012
- Manuscript Revised: 15 OCT 2012
- Manuscript Received: 19 AUG 2012
- flap necrosis;
- ischemia reperfusion injury;
- nuclear factor-kappaB;
- synthetic double-stranded oligodeoxynucleotide
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. Copyright © 2012 John Wiley & Sons, Ltd.