Changes of HIF-1α and VEGF expression induced by hypoxia in rats with brain injury caused by drowning / 第二军医大学学报

ABSTRACT

Objective: To observe the histomorphology/pathology changes and the expression of hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in drowning rats brain, in an attempt to explore new pathways for treatment of water drowning. Methods: The animal model of freshwater drowning was established with rats. The rats were randomly divided into the following groups control group, drowning-to- death group and 2 min-drowning group (including 5 subgroups survived for 3, 6, 12, 24, and 40 hours after being drowned in water for 2 min [n=10]). Brain indices of rats in each group were detected and the pathological changes of cerebral tissues were observed; the expression of HIF-1α and VEGF were detected immunohistochemically and the correlation between them was analyzed. The dynamic blood oxygen saturation was detected in rats survived for 40 h after 2 min-drowning at different points. Results: Brain index of the drowning group and groups surviving for 24, 40 hours after drowning were obviously higher than that of the control group (P<0.05). Brain indices of the drowning-to-death group and the 24 h, 40 h survival groups were obviously higher than that of the control group; and those of the 3 h, 12 h survival groups were obviously lower than that of the drowning-to-death group but higher than that of the normal control group (P<0.05). The blood oxygen saturation was (59=5)% immediately after drowning and then gradually increased and reached the normal level after 12 h. The cerebral edema appeared 3 h after drowning and was gradually aggravated from 12 h to 24 h after drowning, then slightly relieved 40 h after drowning. There was no expression of HIF-1α in the control group and lower expression in drowning-to-death group; the expression of HIF-1α gradually increased with the increase of drowning period and reached peak 12 h after drowning(P<0.05); the expression of VEGF had a similar pattern to HIF-1α. The expression of HIF-1α was positively correlated with that of VEGF(r=0.629,P<0.05). Conclusion: Freshwater drowning can cause serious cerebral injury. The brain can be protected from oxygen deficiency by promoting synthesis of HIF 1α and subsequent upregulation of VEGF expression.