백서 간의 재관류 손상에서 단기간 허혈전처치의 효과 : Interleukin-1α와 Nuclear Factor-κB 발현

Abstract

Background : A short period of ischemia and reperfusion, called ischemic preconditioning, protects various tissues against subsequent sustained ischemic insult. Apoptosis of hepatocytes and sinusoidal endothelial cells are a critical mechanisms of injury in the ischemic liver. Because nuclear factor-κB (NF-κB) has a significant role in the cell survival, we hypothesized that ischemic preconditioning protects by inhibition of apoptosis through the expression of NF-κB, induced by interleukin-1α (IL-1α), which is known for enhancement of its transcription and activation. Methods : We induced ischemia and reperfusion on rat liver, and performed in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labelling assay and polymerase chain reaction for IL-1α mRNA and NF-κB mRNA. Results : Apoptosis of hepatocytes and sinusoidal endothelial cells, assessed by in situ TUNEL assay, was significantly reduced with preconditioning. The expression of IL-1α mRNA and NF- B mRNA are seen on discrete monoclonal bands around 344 and 356 base pairs, in comparison with normal rat liver, but, there was no significant difference between the ischemia-reperfusion group and the preconditioning group. Conclusions : We suggest that ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apotosis through the expression of IL-1α inducing NF-κB and its activation. However, we need further study in the activity of NF-κB, such as nucleotide shift assay, because the activity of NF-κB is regulated by binding of the inhibitory protein, I κB.