Objective To investigate the effect of erythropoietin (EPO) on the expression of integrin-β1 in hippocampus of neonatal rats after hypoxic-ischemic brain damage (HIBD) and to discuss the neuroprotective mechanisms for EPO.Methods Neonatal Sprague-Dawley rats of 7 days old were randomly divided into 3 groups by random number table method (24 cases in each group):sham-operated group,HIBD group and EPO treated group(EPO group),then each group was further divided into 4 subgroups (n=6) based on different time points following the injection of 9 g/L or EPO (6 h,24 h,3 d,7 d).The expressions of integrin-β1 and integrin-β1 gene in hippocampus were determined by Western blot and real-time fluorescent quantitative PCR(RT-qPCR).Results By Western blot method:integrin-β1 had low expression in the hippocampus of the sham-operated group at each time point,which had no significant difference(0.47±0.22,0.45±0.18,0.54±0.24,0.53±0.22,F=.223,P=0.879).The expression of integrin-β1 in HIBD group was increased at first and then decreased,which had a significant difference(0.62±0.16,1.42±0.32,1.13±0.37,0.81±0.21,F=11.809,P=0.000).In the EPO group the expression of integrin-β1 was rising significantly at 24 h and 7 d and showed two peaks (0.64±0.21,1.10±0.37,0.96±0.30,1.19±0.31,F=3.741,P=0.028).Compared with the sham-operated group at corresponding time points,the integrin-β1 protein expression showed significant increase at 24 h and on 3 d in HIBD group and 24 h,3 d,and 7 d in EPO group (all P<0.05).By RT-qPCR:there was no significant difference in the gene expression of integrin-β1 in ippocampus of the sham-operated group at different time points (0.31±0.13,0.33±0.16,0.34±0.15,0.32±0.17,F=0.036,P=0.990).Gene expression of integrin-β1 in HIBD group was increased at first and then decreased and the summit was at 24 h point(0.72±0.35,1.39±0.33,0.95±0.24,0.61±0.25).The difference between each time point was statistically significant (F=8.022,P=0.001).Integrin-β1 gene expression of EPO group showed two peaks at 24 h and on 7 d(0.77±0.30,1.09±0.27,0.90±0.38,1.17±0.36),and there was a significant difference between 6 h group and 7 d group (P<0.05).Compared with the sham-operated group at corresponding time points,the expression of integrin-β1 gene in between HIBD group and EPO group was extremely higher(all P<0.05).Besides,the gene expression of integrin-β1 in EPO group was higher than that in the HIBD group on 7 d with statistically significant difference (P<0.05).Conclusion Erythropoietin can upregulate the expression of integrin-β1 in the recovery phase of HIBD,which may be one of the beneficial effects of EPO for HIBD.