허혈 후 뇌신경계에서 NO에 의한 유전자 발현 조절

초록

The inducible nitric oxide synthesis (iNOS) inhibitor aminoguanidine(AG) reduces ischemic demage in animal model of transient middle cerebral artery occlusion (MCAO). To identify the genes regulated by the AG treatment in MCAO model, which might be responsible for the protective effect of AG, we examined the changes in gene expression patterns in AG-administered animal utilizing cDNA microarray analysis. We focused on the changes of gene expression occurred in cerebral cortex of the postischemic from 12 hours to 4 days in cerebral cortex of rat brain. Among the genes up-regulated more than 2-folds after MCAO, most of the genes were down-regulated by AG administration recovering back to the basal level expression. The suppression of the induction of those genes were accompanied by the reduction of the size of the infarction. It suggested that they might play crucial roles in neuronal damage in postischemic brain, The list of genes which was up-regulated in postischemic brain and suppressed by the AG administration was obtained. Interestingly, we also found the evidence for that the expression of a group of gene was down-regulated by NO in postischemic brain, therefore further up-regulated by AG. We are currently investigating the function of selective genes and their regulation in postischemic brain.