NF-κB p65 involves in reperfusion injury and iNOS gene regulation in skeletal muscle
This study investigated the effects of inhibition of NF-κB activation on microcirculation and inducible NOS expression in reperfused rat cremaster muscle. The muscle from 16 rats underwent 5-h ischemia and 90-min reperfusion. Each rat received NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 150 mg/kg) or phosphate-buffered saline 15 min before reperfusion. Results showed that PDTC treatment had a significant overall increase in muscle blood flow during reperfusion. Blood flow more rapidly recovered to and over baseline in the PDTC-treated group than in controls, with a significant difference at 10-30 min and 70-90 min. Expression of iNOS mRNA had a 167-fold increase from normal in controls, but was significantly (P < 0.05) reduced to a 63-fold increase in PDTC-treated muscles. In addition, PDTC treatment significantly (P < 0.05) decreased a reperfusion-induced increase in activated NF-κB p65 and nuclear p65 protein. Our results suggest that NF-κB is involved in I/R injury and that inhibition of NF-B p65 activation aords protection against I/R injury, perhaps via downregulating expression of iNOS transcription. © 2004 Wiley-Liss, Inc.
Qi, WN; Chaiyakit, P; Cai, Y; Allen, DM; Chen, LE; Seaber, AV; Urbaniak, JR
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