Nuclear factor kappaB (NF-kappaB) is thought to play an important role in the expression of genes expressed in response to ischemia/reperfusion (I/R) injury. In this report, the activation of NF-kappaB in rat skeletal muscle during reperfusion following a 4-h ischemic period was studied. NF-kappaB activation displayed a biphasic pattern, showing peak activities from 30 min to 3 h postperfusion and 6 h to 16 h postperfusion, with a decline to baseline binding activity levels between 3 h and 6 h. Inhibition of NF-kappaB activation was investigated using proline dithiocarbamate (Pro-DTC). NF-kappaB binding activity during reperfusion was significantly reduced by intravenous administration of Pro-DTC. Additionally, Pro-DTC resulted in decreased muscle edema and neutrophil activity, with an increased percentage of muscle survival compared with vehicle controls. These results demonstrate that NF-kappaB is activated during reperfusion in a biphasic manner and that the regulation of the initial phase of NF-kappaB activation affords physiological protection against a severe ischemic stress. Selective inhibition of NF-kappaB during early reperfusion may therefore be a therapeutic intervention for I/R injury.
The purpose of the current study was to determine the effects of vascular endothelial growth factor (VEGF) on muscle flap survival and vascularity in a rat gracilis ischemia-reperfusion model. A total of 12 adult male Wistar rats were divided into two groups (n = 6). The experimental group received the plasmid encoding VEGF(165) cDNA plus lipofectamine (cationic liposome) injected directly to the gracilis muscle following 4 h of ischemia. The control group received lipofectamine only. The viability and vascularity of the flaps were evaluated after 7 days of reperfusion. The data demonstrated that the VEGF plasmid- and lipofectamine-treated muscle flaps had significantly greater total survival and capillary count 7 days after reperfusion compared with the flaps treated only with lipofectamine. These results indicate that VEGF exerts a protective effect on ischemic skeletal muscle flaps.
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