The Effect Of Amphiregulin On Focal Cerebral Ischemia-Reperfusion Injury In Rats

Background: Ischemic stroke is a disease of the nervous system with high mortality,and the treatment is limited.A recent study found that Amphiregulin has the function of promoting tissue repair after injure,it also has the distribution in the brain so we want to explore its effect on ischemic stroke.Objective: To investigate the effects of Amphiregulin(Areg)lateral ventricle injection on focal cerebral ischemia-reperfusion injury in rats and its possible mechanism.Methods: Suture Embolization Method was used to occlude the right middle cerebral artery(MCA)for 2 h to induce transient focal cerebral ischemia.Random table method were used to divide the healthy male adult SD rats into six groups(n=14):Sham operation group(Sham),ischemia/reperfusion group(I/R),vehicle treated group(Vehicle),ischemia combined with Areg treatment group(Areg),ischemia combined with AG1478 treatment group(AG1478),and ischemia combined with Areg plus AG1478 treatment group(Areg+AG1478).Rats in Sham group were only exposed the right carotid artery.In Vehicle,Areg and AG1478 group,rats were received Lateral ventricle injection of BSA(5 ?l),Areg(2 ?g/5 ?l)and AG1478(2.5 ?g/5 ?l),respectively,and then Preparation of focal cerebral ischemia reperfusion injury model(MCAO)after administration of 30 min.Rats in AREG+AG1478 group were injected Lateral ventricle with AG1478,followed by Lateral ventricle treatment with Areg 30 min later,and then were subjected to MCAO.At 24 hours after cerebral artery reperfusion,the cerebral infarction volume,neurobehavioral scores and the number of apoptotic cells in brain tissues were compared between each group.In addition,the phosphorylation levels of EGFR and Akt in ischemic brain tissues were detected at 6 h after reperfusion.Results: Compared with the Sham group,the cerebral infarction volume and apoptotic cell number in brain tissues were all significantly increased,while neurobehavioral scores were all notably decreased in Areg and I/R group(all P< 0.05).However,when compared with I/R group,Areg group had less cerebral infarction volume and apoptotic cell number,and higher neurobehavioral score(all P< 0.05).Furthermore,the phosphorylation levels of EGFR and Akt in Areg group were all higher than I/R group(all P< 0.05).Compared with I/R group,the cerebral infarction volume and apoptotic cell number AG1478 group were increased accompanied by a marked reduction of EGFR and Akt phosphorylation(all P< 0.05).Comparatively,Areg+AG1478group not only had more cerebral infarction volume and apoptotic cell number,but also possessed lower neurobehavioral score and levels of EGFR and Akt phosphorylation than Areg group.Conclusion: Areg treatment can reduce the cerebral infarction volume and apoptotic cells in ischemic brain tissues,and increase the neurobehavioral score via activate EGFR-Akt signal in brain tissues of rats suffering from MCAO.So Areg plays a protective role in focal cerebral ischemia-reperfusion injury.