Expression of heme oxygenase-1 in neonatal rats in hippocampus with hypoxic-ischemic brain damage and protective mechanism of naloxone

Objective:To investigate the expression of heme oxygenase-1(HO-1) in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBD),and expore the possible neuroprotective mechanism of naloxone on HIBD.Methods:Neonatal 7-day SD rats were randomly divided into three equal groups:Group S(sham operation group),Group C(HIBD+nomal saline treatment),Group N(HIBD + naloxone treatment).HIBD models were established by Rice method.All of the groups were further divided into six subgroups(n = 8 in each subgroup) according to the time points 3 h,6 h,12 h,24 h,3 d,7 d,after H/I.Western blot was used to detect the protein level of HO-1.Variation of HO-1 activity in hippocampus was detected by biochemical test.The apoptosis cells in hippocampus were detected by TUNEL.Results:① Expression of HO-1 protein:Western blot showed that the expression of HO-1 in hippocampus in Group S was very low and the same at different time points,but the expressions of HO-1 in hippocampus in Group N,Group C increased markedly from 3 h and reached peak at 24 h post-H/I,then gradually decreased,and almost returned to the original levels 7 d after H/I,but still higher than Group S(P 0.01).The expressions of HO-1 12 h,24 h,3 d,7 d after H/I in Group N were significantly higher than those of Group C(P 0.01).② Variation of HO-1 activity:The variation of HO-1 activity in Group C was increased from 3 h and reached peak at 24 h post-H/I,returned to the original level 7 d after H/I.HO-1 activities 12 h,24 h,3 d after H/I in Group N were significantly higher than those of Group C(P 0.01).③ Apoptotic cells detection:TUNEL staining showed that the numbers of apoptotic cells in Group N,Group C in hippocampus of ipsilateral hemisphere gradually increased at 3 h,peaked at 24 h and decreased at 3 d after H/I,the numbers of apoptotic cells in Group N 24 h,3 d,7 d after H/I were significantly lower than Group C(P 0.01).Conclusion:①The expression of HO-1 in hippocampus increased after H/I injury,HO-1 is involved in the regulation of neuronal apoptosis and implicated in pathophysiological mechanisms of neuronal damage after H/I.②Naloxone has a protective effect on H/I-induced neuronal injure,may exert its neuroprotective mechanisms by increasing HO-1 expression.