Protective Effects And Mechanisms Of Zafirlukast On Focal Cerebral Ischemia-reperfusion In Rats

OBJECTIVE To study the protective effects and possible mechanisms of a leukotriene receptor antagonist zafirlukast on focal cerebral ischemia-reperfusion injury (CIRI) in the rats by reversible middle cerebral artery occlusion (MCAO) model.METHODS MCAO model was produced by intraluminal suture technique, and reperfusion 24h was begun after 2h of occlusion. Zafirlukast was intragastrically administrated at 0h and 12h of the reperfusion. After reperfusion 24h, the extent of neurological deficits was evaluated by Longer's method; the expression of CysLTR1 mRNA was detected by RT-PCR method;the infarct size of the brain and the degree of cerebral edema were measured by Auto CAD image analysis soft ware; the morphological changes of the brain tiusse were observed; the permeability of blood brain barrier (BBB) was measured by using Evans blue(EB) as a labelled compound; the expressions of AQP4 and MMP9 proteins were measured;NO,MDA,MPO,iNOS and GSH-PX level in the brain tissue were detected.RESULTS⑴After 2h of occlusion and 24h of reperfusion, the expression of CysLTR1 mRNA was enhanced;the neurological deficits were evidently observed;the brain infarct size and edema degree were increased; permeability of BBB was enhanced; the changes of the brain histology were appeared and the expressions of MMP9 and AQP4 proteins were increased;the activity of MPO and iNOS were increased, the activity of GSH-PX was decreased, the contents of NO and MDA were increased.⑵Both 20 and 40 mg.kg^-1 doses of zafirlukast can dramatically reduce neurological score, the infarct size and degree of cerebral edema and permeability of BBB comparing with ischemia reperfusion group. Both 20 and 40 mg.kg^-1 doses of zafirlukast can increase the activity of...