Expression Of Hypoxia Inducible Factor-1a And Erythropoietin In The Rat Model Of Brain Ischemic Tolerance

Objective: To investigate the expression of Erythropoietin (EPO) and Hypoxia inducible factor-1a (HIF-1a) in the rat model of brain ischemic tolerance induced by ischemic preconditioning(IP) and the correlativity of EPO with HIF-1a.Methods: One hundred and forty five healthy male wistar rats were divided into three groups randomly, the sham surgery group (SS+SS, n=15), the sham and middle cerebral artery occlusion(MCAO) group (SS+MCAO, n=65 ) and the ischemic preconditioning and MCAO group(IP+MCAO, n=65). The latter two groups were further divided into five subgroups respectively for different preconditioning-ischemia intervals. Models of cerebral ischemic preconditioning and ischemic reperfusion (preconditioning group) were made by twice suture method. For ischemic preconditioning, the rats were given MCAO for 10min. At 1, 3, 7, 14 and 21d after IP, the rats were given the second MCAO(or sham surgery) for 2h followed by 22h reperfusion. The infarct volume was measured by triphenyl tetrazolinm chloride(TTC) staining. The protein of HIF-1a and EPO were detected by method of immunohistochemistry. The expression of HIF-1a mRNA and EPO mRNA were detected by reverse transcriptase polymerase chain reaction(RT-PCR)..Results: (1)The infarct volume in the 1d, 3d and 7d subgroups of IP+MCAO group were significantly smaller compared with that of SS+MCAO group (P＜0.05). (2)The protein expression of HIF-1a in the 1d, 3d, 7d subgroups of IP+MCAO group were significantly higher compared with that of SS+MCAO group (P＜0.05); The protein expression of EPO in the 3d, 7d subgroups of IP+MCAO group were significantly higher compared with that of SS+MCAO group (P＜0.05). (3) The expression of EPO mRNA and HIF-1a mRNA in the 3d, 7d subgroups of IP+MCAO group were significantly higher compared with that of SS+MCAO group (P＜0.05). (4)There were positive correlation between the expression of EPO mRNA and HIF-1a mRNA (r=0.737, P<0.01).Conclusion: The ischemic tolerance of the rat brain was induced by IP. Endogenously produced HIF-1 a and EPO may be essential mediators of cerebral ischemic tolerance. The expression of EPO mRNA were positively correlated with HIF-1a mRNA.