缺氧诱导因子和血管内皮生长因子在大鼠淹溺后脑损伤中的作用

Effects of hypoxia inducing factor-1αand vascular endo-thelial growth factor on brain injury of drowning rats

目的观察淹溺对脑组织缺氧诱导因子(HIF-1α)和血管内皮生长因子(VEGF)的影响及两因子间的相关性,以探讨HIF-1α和VEGF在淹溺所致大鼠脑损伤发生中的病理机制。方法Wistar大鼠70只,随机分为对照组、溺死组和淹溺组,淹溺组又分为淹溺后存活3、6、12、24、40h组。动态检测大鼠血氧饱和度;于相应时间点取各组脑组织测定脑指数;制作病理切片,HE染色后光镜下观察脑组织形态学变化;链霉亲合素—生物素—过氧化物酶连结法检测HIF-1α和VEGF的表达。结果溺死组血氧饱和度显著低于对照组,淹溺组血氧饱和度随存活时间延长逐渐上升,12h后恢复正常。溺死组脑指数较对照组脑指数增加(P<0.05),淹溺组存活3h和12h的大鼠脑指数小于溺死组(P<0.05)。溺死组脑组织疏松,脑细胞水肿;淹溺组亦有脑水肿表现,40h水肿较前略有减轻,但有部分脑细胞变性、坏死和出血。各组间HIF-1α和VEGF表达的差异均具有统计学意义,且两因子表达呈正相关。结论淹溺可致缺氧性脑损伤,HIF-1α在淹溺非致死机体脑中呈高表达,并调节其下游基因VEGF的表达增强,可对脑组织产生保护作用,随着缺氧状态的纠正,两者的表达逐渐下降。

Objective To observe the effects of hypoxia inducing factor （HIF-1α） and vascular endothelial growth factor （VEGF） on brain injury of drowning rats. Methods Seventy healthy Wistar rats were randomly divided into three groups： normal control group, drowned group, and drowning group. The dynamic saturation of blood oxygen was detected, the brain index of each group was calculated, and the morphology changes of brain tissue was studied by the brain paraffin sections stained with hematoxylin eosin. The expressions of HIF-1α and VEGF at every phase of brain injury were detected by immunohistochemistry. Results Compared with normal group, the saturation of blood oxygen was obviously lower in drowned group, but in drowning group, it was increased time-dependently, and regained to normal degree at 12 h after drowning. The brain index of drowned group was higher than control group （P 〈0.05）, and the brain index of drowning group at 3 and 12 h after drowning was smaller than drowned group （P 〈0.05）. Looseness of brain tissue and cerebral edema could be observed in drowned group, and cerebral edema could also be observed in drowning group. Edema was slightly relieved at 40 h after drowning, but it was accompanied with cellular necrosis, degeneration and bleeding. The expressions of HIF-1α and VEGF were significant different among each groups （P 〈0.05）, and the expression of HIF-1α was positively correlated with that of VEGF （P 〈0.05）. Conclusion Freshwater drowning can cause hypoxic brain injury, during this process, HIF-1α expression is upregulaed and its upregulation may upregulate the expression of VEGF. The two kinds of cytokines may play protective roles in brain injury.