| Objective: To investigate the expression of Hypoxia inducible factor-1a (HIF-1a ) and its target gene Erythropoietin (EPO) in the model of brain ischemic tolerance induced by ischemic preconditioning through twice occlusion of middle cerebral artery in rats.Methods: 84 healthy wistar rats were divided into three groups randomly, the sham surgery group (SS+SS, n=4), the sham and middle cerebral artery occlusion(MCAO) group (SS+MCAO ,n=40) and the ischemic preconditioning and MCAO group (IP+MCAO ,n=40) . Firstly, we built the rat model of focal ischemic preconditioning;then, we gave another ischemia of 2 hours at the time of ld,3d,7d,14d,21d after ischemic preconditioning;finally, we measured the infarct volume, detected the expression of the HIF-la and its target gene EPO ,and evaluated the pathology damage by HE staining.Results: The results of infarct volume showed that the infarct volume in the ld,3d and 7d subgroups of IP+MCAO group were161.2±6.9mm~3 134.9±9.0mm~3 142.9±13.7mm~3 respectively, and they were significantly smaller compared with that of the SS+MCAO groups (p<0.05).The results of immunohistochemistry showed that the MOD of HIF-la in the ld,3d,7d subgroups of IP+MCAO were 125.93±3.79,140.63±4.64,131.15±2.74 respectively, and they were significantly higher compared with that of the SS+MCAO groups (p <0.05);the MOD of EPO in 3d,7d subgroups of IP+MCAO were 141.68±3.29,138.88±2.59 respectively, and they were significantly higher compared with that of the SS+MCAO groups (p<0.05).Conclusion: The ischemic tolerance of the rat brain was induced by transient focal ischemic preconditioning , proved by the diminution of infarct volume and the pathological changes of brain tissue. The protein expression of HIF-1 α and its target gene EPO were up-regulated, according with the time course of ischemic tolerance. The neuroprotective effect of ischemic tolerance was correlated with the expression of HIF-1 α and its target gene EPO.
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