The Relationship Between COX-2 Expression And Brain Injury In Global Cerebral Ischemia Reperfusion Rat

Aim:To investigate the relationship between COX-2 expression and brain injury in global cerebral ischemia reperfusion(IR)rat. Methods:(1)The rat model of global cerebral ischemia reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension. After IR 30min,2h,6h,24h,48h,7d,15d and 30d , the expression of COX2 and NF-κBp65 were detected, respectively.Meloxicam (1 , 3 and 5 mg·kg^-1) was intraperitoneally administered 30 min before the operation in IR 7d rats.(2)The related indexes were detected:Morris water maze was used to evaluate the ability of spatial learning and memory function.HE staining was used to observe pathomorphological changes of hippocampal neurons.NF-κB p65 and COX-2 expression was detected by immunohisto- chemistry and immunfluorescent staining , SOD activities and MDA contents were analyzed by biochemistry.The expression of COX-2 mRNA and protein in rats hippocampal neurons were also measured by the methods of RT-PCR and Western-Blot.Results:Compared with that of the sham group,the spatial learning and memory function of IR rats were significally impaired.Hippocampal neurons in model rats showed obviously karyopycnosis and loss,and reach the peak at 48 hours-7d. The expression of COX-2 mRNA and protein as well as NF-κBp65 protein in rat hippocampi obviously increased.Meloxicam remarkably improved the spatial learning and memory function,obviously prevented the hippocampal neurons from karyopycnosis and losing induced by IR.Meloxicam significantly blunted the increase of MDA content,NF-κBp65 protein expression,and the decrease of SOD activities in IR rats. The expression of COX-2 mRNA and protein was significantly down-regulated in hippocampus of IR rats by Meloxicam.Conclusions:COX-2 expression takes part in pathophysiological process of neuronal injury induced by IR.Meloxicam has an obviously neuroprotective effect on global cerebral ischemia reperfusion damage.The action of inhibiting COX-2 activity,decreasing COX-2 mRNA and protein,decreasing the production of PGs may be involved in the protective mechanism.