Effect of parecoxib pretreatment on expression of aquaporin-4 during focal cerebral ischemia-reperfusion in rats

Objective To investigate the effect of parecoxib pretreatment on the expression of aquaporin-4 (AQP4) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods One hundred and twenty-eight adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 230-280 g,were randomly divided into 4 groups (n =32 each):sham operation group (S group),I/R group,parecoxib 5 mg/kg group (group P5) and parecoxib 10 mg/kg group (group P10).The rats were anesthetized with 10％ chloral hydrate 3.5 ml/kg.Focal cerebral I/R was induced by 2 h middle cerebral artery occlusion followed by reperfusion.Parecoxib 5 and 10 mg/kg were injected via the right internal jugular vein at 30 min before middle cerebral artery occlusion in groups P5 and P10,respectively.The equal volume of normal saline was injected instead of parecoxib in groups S and I/R.Neurological deficit score (NDS) was assessed at 2 and 24 h of reperfusion.The rats were then sacrificed and brains were removed for determination of infract volume (by TTC staining).Brain water content was measured by wet/dry brain weight ratio.Their brains were cut into sections which were stained with haematoxylin and eosin and examined under microscope.The expression of AQP4 in brain tissues was measured.Results Compared with S group,NDS and brain water content were significandy increased,the infarct volume was enlarged,and the expression of AQP4 in brain tissues was up-regulated in I/R group (P ＜ 0.05 or 0.01).NDS and brain water content were significantly lower,the infarct volume was smaller,and the expression of AQP4 in brain tissues was lower in groups P5 and P10 than in I/R group (P ＜ 0.05 or 0.01).Microscopic examination showed that brain injury was significantly attenuated in groups P5 and P10 as compared with I/R group.Conclusion The mechanism by which parecoxib pretreatment alleviates the focal cerebral I/R injury in rats is related to down-regulation of the expression of AQP4. Key words: Cyclooxygenase inhibitors;  Reperfusion injury;  Brain;  Aquaporin 4