Objective To investigate the effect of 2-methoxyestradiol(2ME2)on the expressions of hypoxia-inducible factor 1α and apoptosis-related genes(RTP801 and caspase-3)in the hippocampus of rats following global cerebral ischemia.Methods A total of 168 adult male SD rats were randomized into 2 groups,global cerebral isehemia group(GI group,n=84)and global cerebral ischemia+2ME2 treatment group(GI+2ME2 group,n=84).In GI and GI+2ME2 groups,4 vessel occlusion(4-vo)global ischemia was induced,and the rats were sacrificed at 6,12,24,48,96h,and 5 and 7 days after the reperfusion.Nissl staining was used for quantitative analysis of the hippocampal neurons,and immunohistochemistry and RT-PCR were performed to detect the expressions of HIF-1α protein,caspase-3 protein and RTP801 mRNA.Results At 48,96h and 5 and 7 days after the reperfusion,the numbers of hippocampal neurons in GI+2ME2 group were 37.09±3.52,26.93±3.10,22.22±3.091,and 6.98±3.07,respectively,significantly higher than those in GI group(P＜0.05).2ME2 significantly suppressed the expression levels of HIF-1α and reduced the numbers of the cells positive for HIF-1α protein to 1 1.47±1.9,20.27±2.07,3.12±0.89,1.07±0.83 at these time points(P＜0.05).The expressions of caspase-3 protein were decreased significantly in GI+2ME2 group,with the numbers of positive cells of 12.39±1.67,20.65±2.01,15.61±1.26,and 6.57±1.12 at the time points.The absorbance of RTP801 mRNA expression at the time points from 12 h to 5 days in GI+2ME2 group was 0.750±0.078,1.008±0.090,0.717±0.072,0.43 1±0.047,and 0.23 1±0.028,respectively,significantly lower than that in GI group(P＜0.05).Conclusion 2ME2 offers brain protection in rats with global cerebral ischemia and suppresses the elevation in the expressions of hypoxia-inducible factor 1α,RTP801 and caspase-3.