Temporal changes of HIF-1α and rat brain hippocampus injury induced by acute hypobaric hypoxia

ZHANG Wenbin; SU Chang; ZHANG Yongliang; LI Jianyu; LI Lingzhi

doi:10.3969/j.issn.1002-266X.2016.04.003

Abstract：Objective To observe the temporal changes of hypoxia-inducible factor-1α( HIF-1α) in rat brain hippo-campus after acute hypobaric hypoxia and to explore the relationship between the changes and brain injury. Methods We randomly divided 100 male SD rats into the normoxic control group and hypoxia injury groups. The rats of hypoxia injury groups were further divided into four subgroups (6 h, 12 h, 18 h and 24 h) on the basis of the duration in hypobaric hy-poxia and 20 rats in each group. Except the control group, other four subgroups were placed in hypobaric chamber imitating a plateau of 7000 meters. After hypobaric hypoxia injury, the morphological changes of hippocampus were observed by HE staining. The brain water content, the level of NO and the activity of nitric oxide synthase ( NOS) were detected. The ex-pression of HIF-1α mRNA was detected by RT-PCR and HIF-1α mRNA protein was detected by immunofluorescence stai-ning. Results ①Compared with the control group, after hypobaric hypoxia, the neurocytes in the hippocampus showed varying degrees of swelling, necrosis, apoptosis and karyorrhexis or karyolysis. The cytoplasm was stained with inhomoge-neous oxyphilic red colour. The CA1 in hippocampus was more sensitive to hypobaric hypoxia than the others. ②Compared with control group, the brain water content was significantly increased in a time-dependent manner in the subgroups ( all P<0.01). ③Compared with the control group, the activities of NOS in each subgroup was increased (all P <0. 01). Meanwhile, except the 6 h group, the levels of NO in each subgroup was increased in a time-dependent manner ( all P<0. 01). ④The expression of HIF-1α mRNA was not detected in the control group. Compared with the control group, the expression of HIF-1α was significantly increased with a time-dependent manner in the subgroups (P<0. 01 or P<0. 05). The results of immunofluorescence showed no green fluorescence of HIF-1αprotein was found in hippocampus of the control group. After hypobaric hypoxia, a weak green fluorescence appeared in part of cytoplasm at first, but with prolonged hypox-ia time, a gradually enhanced fluorescence was observed and it showed a trend of aggregating to the nucleus. Conclusions Acute hypobaric hypoxia increased the brain water content and led to cerebral edema and the extent of damage was aggra-vated with prolonged hypoxia time. Stressful expression of HIF-1αplayed an important role in protective regulation of cere-bral injury induced by acute hypobaric hypoxia.