Aim To investigate the therapic effects of Pae on brain ischemia-reperfusion injury in rat.To observe neurological scores,oxidative stress, blood brain barrier injury, infarct size and explore the mechanism of action of Pae, as well as, we want to know whether PI3K/Akt pathway is the molecular biology mechanism of healing ischemia-reperfusion injury on Pae.METHODS Establish middle cerebral artery occlusion (MCAO) model.Duodenum injection with Pae(150、 75、37.5mg /kg) after ischemia, and using Tanakan as the positive control drug.24h after the reperfusion, grading neurological scores; assaying SOD, GSH-PX, MDA, tNOS, iNOS and NO in ischemic hemi-brain with XO method; analyzes the expression of MMP-9 in hippocampus using western blotting.Middle cerebral artery occlusion (MCAO) model was established by suture-occluded method, 24 rats were then randomized into 4 groups for treatment with sham、 model、 DMSO+Pae (150mg/kg)、 LY294002(20mmol/L) +Pae (150mg/kg).PI3K/Akt pathway inhibitor (LY294002) or DMSO was injected into the ventricular space on the ischemic side 1h before ischemia.24h after the reperfusion, grading neurological scores, the infarct size was measured by TTC staining; the PI3K, Akt and P-Akt expression in hippocampus was analyzed by western blotting.RESULTS Compared with the model group, Pae (150、 75mg/kg) evidently decrease neurological scores of Brain I/R rats.It manifests that Pae have effects to reduce the injury of nervous system.Pae (150、 75、 37.5mg/kg) can notably increase the SOD and GSH-PX concentration in ischemic hemi-brain, as well as decrease the MDA,NOS and NO.It indicates that Pae could inhibit brain I/R induced oxidative injury.The results of western blotting displayed that compared with the model group, Pae (150、 75mg/kg) evidently decrease the expression of MMP-9 in hippocampus of Brain I/R rats.It indicates that Pae have effects to reduce theinjury and the permeability of blood brain barrier.The infarct size was significantly reduced in the DMSO+Pae(150mg/kg)group.The infarct size of LY294002+Pae(150mg/kg)group is evidently increased.It manifests that the Pae could ameliorate I/R injury, and the mechanism of this neuroprotective effect involves the preservation of PI3K/Akt pathway activity.The results of western blotting displayed that compared with the model group, The expression of P-Akt of DMSO+Pae (150mg/kg) group is evidently increased and the expression of P-Akt of LY294002+Pae (150mg/kg) group is lower than DMSO+Pae (150mg/kg) group, meanwhile, The expression of PI3K and Akt is no significant difference was found.The result illustrates that Pae could activate PI3K/Akt signaling pathway, mainly increases the expressionof P-Akt to bring the neuroprotection on brain I/R rats.CONCLUSIONS It was obviously that Pae could ameliorate acute oxidative injury which was induced by brain I/R in rat.The neuro-protective mechanism is considered to be related to protecting endogenous anti-oxidant, getting rid of free radical and protecting blood brain barrier.Pae could activate PI3K/Akt signaling pathway, especially increases the expression of P-Akt to restrain the death of nerve cell and then decreases the infarct size.The inhibitor of PI3K/Akt pathway could block neuroprotection of Pae.