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Transfection of nuclear factor‐kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model
Author(s) -
Uemura Takeshi,
Tsujii Masaya,
Akeda Koji,
Iino Takahiro,
Satonaka Haruhiko,
Hasegawa Masahiro,
Sudo Akihiro
Publication year - 2012
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2677
Subject(s) - decoy , transfection , tumor necrosis factor alpha , reperfusion injury , ischemia , nitric oxide synthase , group a , fluorescein isothiocyanate , nitric oxide , microbiology and biotechnology , medicine , immunology , chemistry , biology , biochemistry , receptor , physics , quantum mechanics , fluorescence , gene
Background 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. Methods 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). Results 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. Conclusions 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.