Abstract: Objective To observe the changes of ischemic preconditioning on the expression of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in ischemia hippocampus CA1 region after focal cerebral ischemia/reperfusion (I/R) in rats, and the mechanisms of brain protection from brain ischemia preconditioning (BIP) thereof. Methods The male SD rats were randomly divided into three groups： sham operation (SO) group， middle cerebral artery occlusion (MCAO) group and brain ischemia preconditioning (BIP) group. The MCAO group and BIP group were further divided into six subgroups according to perfusion time after I/R including 2 h, 6 h, 12 h, 24 h, 48 h and 72 h. The ischemia preconditioning model rats were established. Immunohistochemistry and Western blot assay were used to observe the expressions of HIF-1α and VEGF in ischemia hippocampal CA1 region. Results Neurological function deficit was not observed in SO group. Compared with MCAO group, there was a lower neurological function deficit score in BIP group. In MCAO group and BIP group, the expressions of HIF-1α and VEGF positive cells and protein increased at 2 h after I/R, then gradually increased from 6 h to12 h and reached the maximum level at 24 h, then gradually decreased. The levels were still higher at 72 h than those of SO group. The number of HIF-1α and VEGF positive cells and protein were significantly increased in MCAO group and BIP group than that of SO group (P < 0.05). The number of HIF-1α positive cells was higher in BIP group than that in MCAO group except 2 h and 6 h reperfusion groups. The expression of VEGF positive cells, HIF-1α and VEGF protein were significantly higher in BIP group than those in MCAO group at different time points (P < 0.05). Conclusion Ischemic preconditioning plays a protective role in brain, which may be related to up-regulation of HIF-1α and VEGF.

Key words: hypoxia-ischemia, brain, aryl hydrocarbon receptor nuclear translocator, vascular endothelial growth factors, HIF-1α, VEGF