Expression of Hypoxia Inducible Factor-1α and Erythropoietin in the Rat Model of Brain Ischemic Tolerance

Objective To investigate the expression of hypoxia inducible factor-1α(HIF-lα) and its target gene erythropoietin(EPO)in the rat model of brain ischemic tolerance induced by ischemic preconditioning(IP). Methods Eighty-four healthy Wistar rats were enrolled randomly into three groups for different pretreatments, the sham surgery group(SS+SS,n=4), the sham and middle cerebral artery occlusion(MCAO) group(SS+MCAO, n=40) and the IP and MCAO group(IP+MCAO, n=40). The latter two groups were further divided into five subgroups due to different IP. The rats were given MCAO for 10 minutes for IP. At 1, 3, 7, 14 and 21d after IP, the rats were given the second MCAO(or sham surgery) for 2 hours followed by 22 hours reperfusion. The infarct volume was measured by triphenyl tetrazolinm chloride(TTC) staining and we detected the protein of HIF-1α and EPO by immunohistochemistry. Results ⑴The infarct volumes in the 1 d, 3 d and 7 d subgroups of IP+MCAO were significantly smaller than those of the SS+MCAO subgroups(P0.05). ⑵The expressions of HIF-1α protein in the 1 d, 3 d and 7 d subgroups of IP+MCAO were significantly higher than those of the SS+MCAO subgroups(P0.05), while the expressions of EPO protein in the 3 d and 7 d subgroups of IP+MCAO were significantly higher than those of the SS+MCAO subgroups(P0.05). Conclusion Ischemic preconditioning for 10 minutes induces relative tolerance to subsequent MCAO as evidenced by reduction of infarct volumes. Endogenously produced HIF-lα and EPO may be essential mediators of cerebral ischemic tolerance.