The Study On The Action Mechemism Of Cyclooxygenase-2 Inhibitor For Focal Cerebral Ischmic Reperfusion In Rats

【Objective】1.To explore the protective mechamism of COX-2 inhibitor in rats subjected to focal ischmia/reperfusion. 2.To observe the effect of COX-2 inhibitor on the expression of vascular endothelium growth factor in rats following focal cerebral ischemia/ reperfusion. 【Methods】MCAO for 1.5 h reperfusion Wistar rats models were performed with the photothrombotic occlusion method which were randomly divided into sham-operation group,Vehicle group,Celecoxib 2.5mg/kg group and Celecoxib 25mg/kg group.saline or different doses of Celecoxib were ig administrated to rats respectively after ischemia 30min. The neuroprotection of Celecoxib was observed at 24h timepoint after ischemic reperfusion in rats by detecting the dynamic changes of metabolitic production of Prostaglandin,MDA,SOD in frontal and parietal cortexs and its effect on the VEGF expression in rats among different groups. 【Results】1.The protective mechenisms of COX-2 inhibitor in rats subjected to focal ischemic reperfusion(1)The protective role in CIRI:The cerebral pathologic injury and cerebral edma were distinctly alleviated after rats were treated with Celecoxib,especially remarkable when treated with 25mg/kg of Celecoxib(.2)The dynamic changes of PGE₂,TXB₂,6-K-PGF_1α,the ratio of TXB₂/6-K-PGF_1α,MDA and SOD:The expression of PGE₂,TXB₂,6-K-PGF_1α in frontal and parietal cortexs of rats in Vehicle group peaked at 12～24h and decreased after wards but remained higher level till 72h timepoint. The ration of TXB2 and 6-K-PGF_1αreached its highest point at 24h timepoint and the contents of PGE₂,TXB₂,6-K-PGF_1αwere higher in frontal and parietal cortex, the content of MDA reached its peak at 6～12h post reperfusion and then declined .The activity of SOD reached its lowest level at 6～12h after reperfusion and then increased gradually and there was no statistically difference compared with rats treated with saline at 72h timepoint. (3)the influence of different doses of Celecoxib on PGE₂,TXB₂,6-K-PGF_1α,the ration of TXB)2 and 6-K-PGF_1α,MDA and SOD: Both 2.5mg/kg and 25mg/kg Celecoxib could reduce the accumulation of PGE₂,TXB₂,6-K-PGF_1α in frontal and parietal cortexs to some extent, especially pronominent at 24h timepoint,but at the same time the ratio of TXB₂ and 6-K-PGF_1αdropped.The content of MDA was decreased but that of SOD was increased, especially distinct at 12 timepoint and treated with 25mg/kg of Celecoxib.2.The effect of COX-2 inhibitor on the expression of VEGF in rats following focal cerebral ischemic reperfusion: The positive cells begun to increase at 6-12h timepoint and peaked at 24h timepoint , remaining higher level at 72h timepoint.There was minimal expression in controlateral non-Ischemic of rats at 6h timepoint but less than the ischemic hemisphere.The expression of VEGF at different timepoints prominently located around the infract core and there was a spot of positive cells in the infract core.Except at 6h timepoint, the different doses of Celecoxib could reduced the positive cells in penumba at 12h,24h,48h,72h post reperfusion. The content of PGE2 in the brain was related to the expression of VEGF. 【Conclusions】1.The possible action mechamism of COX-2 in CIRI: (1)COX-2 was implicated in cerebral ischemic reperfusion injury by probably affecting the metabolism of Prostaglandin, altering the ratio of TXB₂ and 6-K-PGF_1α and promoting the production of oxygen radicals. (2)COX-2 was probably implicated in angiogenesis through altering the VEGF expression. 2.The role of COX-2 inhibitor in CIRI:COX-2 inhibitor provided protection against CIRI at the acute phase possibly by reducing the accumulation of PGE₂, the production of oxygen radicals, altering the ration between TXB₂ and 6-K-PGF_1αand increasing the activity of SOD.