The Role of HIF-1α in Neuronal Apoptosis after Hypoxia/Hypoxia Ischemia Brain Damage in Neonatal Rats

Objective To investigate the relationship between HIF-1α expression and neuron apoptosis in hypoxia/hypoxia ischemia brain injury and elucidate the role of HIF-1α in regulating neuron apoptosis.Methods Postnatal day 10 SD rats were divided into three groups: the hypoxia ischemia group(HI),the hypoxia group and sham controls.Rat brains were collected at 4 h,8 h and 24 h after hypoxia from each group.Immunohistochemistry was used to detect the protein expression of HIF-1α and actived caspase-3.Apoptosis positive cells were determined by TUNEL staining.HE staining was used to detect histopathological damage.Results The expression of HIF-1α protein was significantly upregulated at 4 h,peaked at 8 h,and decreased at 24 h after hypoxia/HI.The expression level of HIF-1α protein in hypoxia/HI group was much higher than that in sham controls(P0.01).The expression of activated caspase-3 protein was increased at 4 h and 8 h after hypoxia/HI and significantly upregulated at 24 h,but in sham controls the activated caspase-3 protein remains at a very low level(P0.01).TUNEL staining showed that positive cells significantly increased at 24 h after hypoxia/HI.HE staining showed that neuronal degeneration and edema became prominent at 24 h after hypoxia/HI.The expression of HIF-1α protein was higher in hypoxia groups than that in hypoxia ischemia groups at the same time points(P0.05).However,the expression of activated caspase-3,the number of TUNEL positive cells and the degree of histopathological damage were lower in hypoxia groups than that in hypoxia ischemia groups at the same time points(P0.05).Conclusions The variation tendency of HIF-1α and activated caspase-3 expression was opposite,and the expression of HIF-1α protein and histopathological damage degree was inverse correlation in HIBD.Therefore,it suggested that HIF-1α may play a protective role in neuron after hypoxia/HI.