Expression Of ICEmRNA, COX-2 Protein After Hypoxic-Ischemic Brain Damage In Neonatal Rat And The Anti-oxidation Effect Of COX-2 Specific Inhibitor NS398

Objective In our study, we measured the expression of ICEmRNA, COX-2 protein in cerebral cortex of neonatal Wistar rats with HIBD and compared the changes of MDA, SOD and NO between HIBD neonatal rats and those NS398 was given to, in order to investigate the effect of ICE and COX-2 in the pathogenisis of neonatal HIBD and provide a new theory base and therapeutic way for neonatal HIBD.Methods 1 Groups for measuring the expression of ICEmRNA: Seven-day-old Wistar rats were randomly divided into groups of sham-operation, HIBD12h, HIBD24h, HIBD3d and HIBD 4d, six pups in each group. We measured the expression of ICEmRNA by RT-PCR.2 Groups for measuring the expression of COX-2 protein: Seven-day-old Wistar rats were randomly divided into groups of sham-operation, HIBDSh, HIBD6h, HIBD12h, HIBD24h, HIBD48h and HIBD5d, six pups in each group. We measured the expression of COX-2 protein by immunohistochemistry, and at the same time microscopical changes were observed.3 Groups for comparing the changes of MDA, SOD and NO: Seven-day-old Wistar rats were randomly divided into groups of sham-operation, HIBD, treated with NS398 befpre hypoxia and treated after hypoxia. Each treated group was then divided into groups of high, middle and low dose. MDA, SOD and NO were assayed to analyze their changes between HIBD and treated groups.RESULTS 1 Groups for measuring the expression of ICEmRNA: ICEmRNA was observed both in control and HIBD groups. The expression of ICEmRNA in ischemic cortex began to increase at HIBD12h, peaked at HIBD4d (P<0.01). 2 Groups for measuring the expression of COX-2 protein: COX-2protein was occasionally observed in control animals. In HIBD rats, the expressions of COX-2 protein began to increase at 3h, peaked at 24h (P<0.01), and decreased at 48h-5d significantly (P<0.01). There was an association between upregulation of COX-2 protein and the extent of ischemic neuronal damage.3 Groups for comparing the changes of MDA, SOD and NO: MDA and NO in the hemispheres of neonatal rats with HIBD were higher significantly (PO.01), and SOD was lower significantly (P<0.01) than that in the those of controls. In the treated rats with specific COX-2 anagonist NS398, MDA and NO decreased and SOD increased in some extent, but they were still different significantly (P<0.01) with results in control animals.Conclusions 1 ICEmRNA, COX-2 protein both increassed in neonatal rats with HIBD, and the expression of COX-2 protein was consistent with neuronal changes observsd by microscopy. These results suggested that both ICE and COX-2 had an important role in the pathogenisis of neonatal HIBD.2 MDA, NO decreased and SOD increased in ischemic hemispheres of neonatal rats with HIBD after given specific COX-2 antagonist NS398.These suggested that NS398 had some effect of anti-oxidation. Thus we could conclude that COX-2 might contribute to the pathogenisis of neonatalHIBD by producing oxygen free radicals.