RESUMO
Objectives To observe the effect of amphiregulin (Areg) via lateral ventricle injection on focal cerebral ischemia/reperfusion (I/R) injury in rats and to investigate its possible mechanism. Methods A total of 96 3-month old health specified pathogen free SD rats were randomly divided into 6 groups (n=16 in each group):sham operation group (sham group),only exposure of common carotid artery and bifurcation;I/R group,making I/R model;solvent control group,lateral ventricle injection of standard protein solution(5 μl);Areg group,lateral ventricle injection of Areg(2 μg/5 μl);AG1478 group [AG1478,a blocker of Areg receptor epidermal growth factor receptor(EGFR),lateral ventricle injection of AG1478 (2.5 μg/5 μl);Areg combined AG1478 (AAG) group,lateral ventricle giving AG1478 (2.5 μg/5 μl),and then giving Areg (2 μg/5 μl) after 30 mm.The model of focal cerebral I/R injury was induced after 30 min administration of the above last 4 groups.After 24 h of reperfusion,the volume of cerebral infarction, the neurobehavioral score and the number of apoptotic cells in the brain tissue were compared among the groups. After 6 h of reperfusion,the phosphorylation levels of EGFR and protein kinase B(Akt)in ischemic brain tissue were detected. Results Compared with the sham group,the cerebral infarction volume and the number of apoptotic cells in brain tissue were increased significantly,while the neurobehavioral score was decreased(all P<0.05).Compared with the I/R group,the volume of cerebral infarction,the number of apoptotic cells in the brain tissue were decreased significantly,and the neurobehavioral score was increased in the Areg group,the levels of EGFR and Akt phosphorylation were significantly higher (all P <0. 05). Compared with the I/R group,the volume of cerebral infarction and the number of apoptotic cells of the AG1478 group were increased,the levels of EGFR and Akt phosphorylation were decreased(all P<0.05);Compared with the Areg group,the volume of cerebral infarction and the number of apoptotic cells of the AAG group and AG1478 group were increased significantly,and the levels of EGFR and Akt phosphorylation were decreased significantly(all P<0.05). Conclusions Areg reduces the infarct volume in ischemic brain tissue,improves nerve function,and inhibits apoptosis by activating EGFR-Akt signaling pathway. Therefore,it has some protective effect for cerebral I/R injury.