Protective Effect of a Nuclear Factor-Kappa B Inhibitor on Ischemia-Reperfusion Injury in a Rat Epigastric Flap Model

ABSTRACT

We examined whether nuclear factor-kappa B (NF-κB) activation was involved in the ischemia-reperfusion (I/R) injury in a rat skin flap model and whether administration of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, could improve flap viability. Eighty-four Sprague-Dawley rats were divided into control group (n = 28), I/R group (n = 28), and PDTC-treated group (n = 28). An abdominal skin flap (4 × 5 cm) was elevated and subjected to 10 hours of ischemia in both the I/R group and the PDTC-treated group. A bolus of PDTC (300 mg/kg) was infused 5 minutes before reperfusion, followed by a second dose during the first 30 minutes of reperfusion in the PDTC-treated group. Flap tissues were assessed by electrophoretic mobility shift assay at 1, 2, 3, and 6 hours of reperfusion, and myeloperoxidase activity and neutrophil infiltration were assessed at 12 hours of reperfusion. The viability of flaps was assessed 7 days postoperatively. NF-κB was activated after reperfusion in the I/R group and displayed peak activity at 1 and 3 hours of reperfusion. In the PDTC-treated group, NF-κB activity was significantly reduced at 1, 2, and 6 hours of reperfusion. Myeloperoxidase activity was significantly decreased, and little neutrophil infiltration could be observed. In the PDTC-treated group, the survival of flaps was 86.88 ± 13.63%, which was significantly greater than the I/R group, in which only 19.20 ± 7.52% of the flap survived. NF-κB is activated during reperfusion in a rat skin flap I/R model. Administration of PDTC can significantly improve flap survival by regulating the early activation of NF-κB and suppressing neutrophil infiltration within the flap.

KEYWORDS

Surgical flaps - reperfusion injury - nuclear factor-kappa B - neutrophil

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