Expressions Of MMP-9 And COX-2 After Focal Cerebral Ischemia Reperfusion Injury And The Effects Of Celecoxib In Hyperlipidemic Rat

Objective:To investigate the expressions of cyclooxygenase-2(COX-2) and matrix met- alloproteinase-9(MMP-9) after focal cerebral ischemia reperfusion(IR) injury in hyperlipidemic (HL) rat,To observe the infarction volume and the morphologic change after middle cerebral artery occlusion(MCAO)in hyperlipidemic rat.To investigate the effects of Celecoxib on the expressions of cyclooxygenase-2(COX-2) and matrix metalloproteinase-9(MMP-9),the infarc- tion volume after focal cerebral ischemia-reperfusion(IR) injury in hyperlipidemic(HL) rat.To explore the effect of hyperlipidemia and Celecoxib after focal cerebral ischemia reperfusion injury rat.Methods:The 70 wistar rats were randomly divided into two groups:non-hyperlipidemia group (n=30);hyperlipidemia group (n=40).After the hyperlipemic rats were made,non-hyperli- pidemia group were randomly divided into two groups: sham-operated group(S group,n=10); non-hyperlipidemic ischemia reperfuion group(nIR group,n=20); hyperlipidemia group were randomly divided into two groups: hyperlipidemic ischemia reperfusion group (hIR group,n= 20);Celecoxib treatment and hyperlipidemic ischemia reperfusion (C+hIR group,n=20).The latter three were further divided into three subgroups according to reperfusion time interval of 12h,24h,and 48h after brain ischemia(5,10,5 rats in each subgroups respectively).Using modified method to make focal cerebral ischemia reperfusion model.Celecoxib in C+hIR group were administrated intragastrically 1 hour after ischemia(25mg/kg,twice a day),The same amount of saline in other groups were administrated.Immunohistochemical staining were used to measure the expressions of MMP-9 and COX-2 in the brain tissue,HE staining were used to observe the morphologic change.The infarction volume was observed by 2,3,5-triphenyltetra- zolium(TTC) stain at the time point of 24h after reperfusion.Results:(1)The hyperlipemic rat model was made by high-fat forage sueeessful,MCAO established by inserting nylon thread coated with paraffin is a good ischemia and reperfusion model.(2)In the time point of 24h after reperfusion, compared with in nIR group,the infarction volume in hIR group was larger and the difference was significant(P<0.01);compared with in hIR group, The infarction volume in C+hIR group were decreased (P<0.01). (3)The expressions of MMP-9 and COX-2 in brain tissue of IR groups were higher than in the S group(P<0.01).In the same IR time subgroup,the expressions of MMP-9 and COX-2 in hIR group were more than in nIR group(P<0.01). compared with in hIR group, the expressions of MMP-9 and COX-2 in C+hIR group were decreased (P<0.01). (4)The expression of MMP-9 was correlated with expression of COX-2 in time.Conclusion:(1)The expressions of MMP-9 and COX-2 is upgraded in ischemical reperfu- sion injury.(2)Hyperlipemia probably aggravate the ischemical reperfusion injury by increasing the expressions of MMP-9 and COX-2, the infarction volume.(3)Celecoxib may recede the expression of MMP-9 by the inhibition of COX-2,and interfere with the inflammatory response which plays the important role in the pathological progress of cerebral ischemia-reperfusion injury in hyperlipidemic rat,thus attenuate the cerebral ischemia-reperfusion injury。...