[Neuroprotective effects of combined application of JAK-STAT signal pathway inhibitor and free radical scavenger on focal cerebral ischemia/reperfusion injury in rats].

：Objective To investigatethe neuroprotective effects and dose-response relation by combining JAK-STAT signalpathway inhibitor(AG490)with free radical scavenger dimethylthiourea (DMTU)in ratssubjected to focal cerebral ischemia/reperfusion(I/R)injury.Methods In all rats,the middlecerebral artery occlusion(MCAO)was produced by occlusion of right internal carotid arterywith a nylon monofilament.One hundred male Sprague-Dawley(SD)rats were divided into tengroups according to random digits table,10 rats were in each group.The first experimentinvolved I/R modeI controI,dimethyl sulfoxide(DMSO)control,normaIsaline(NS)control,AG490,DMTU and combination of AG490 and DMTU(A+D)groups.The secondexperiment involved model group and three experimental groups in which various doses ofDMTU and AG490 were administered.The neurological behavior scores(NBS)were assessed at24,48 and 72 hours after reperfusion respectively in both experiments,and all the animalswere then decapi rated to determine the brain infarct volume after 72 hours.Results Thevalues of NBS in A+D group,AG490 group and DMTU group were higher than those in modelgroup at 24,48 and 72 hours after I/R,and their brain infarct volumes were obviouslysmaller than model group as well(all P＜0.05).The brain infarctvolume in A+D group was obviously smaller compared with AG490 and DMTU alone(all P＜0.05).Thevalues of NBS were higher and the brain infarct volumes were smaller in both high dose andmedium dose combination groups than those in low dose combination and model groupsrespectively(all P＜0.05).In addition,brain infarct volumes in high dosegroup were smaller than medium dose group(P＜0.05),but there was no statistically significantdifference between low dose and model groups.Conclusion The combined application of AG490and DMTU produces a dose-dependent synergistic neuroprotective effect. Key words: cerebral ischemia/reperfusion injury; JAK-STAT signalpathway; free radical scavenger; dose-response relation