Protective effect of a nuclear factor-kappaB inhibitor on ischemia-reperfusion injury in a rat epigastric flap model.
We examined whether nuclear factor-kappa B (NF-kappaB) 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-kappaB 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 x 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-kappaB 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-kappaB 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-kappaB 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-kappaB and suppressing neutrophil infiltration within the flap.
Wu
Xiaowei
X
Renmin Hospital of Wuhan University, Wuhan City, PR China.
Yu
Mosheng
M
Li
Ailin
A
D000704:Analysis of Variance; D000818:Animals; D024202:Electrophoretic Mobility Shift Assay; D019074:Epigastric Arteries / Q000601:surgery*; D006085:Graft Survival / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013524:Surgical Flaps / Q000098:blood supply*; D013859:Thiocarbamates / Q000494:pharmacology*
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D009195:Peroxidase