高压氧干预对大鼠脊髓继发性损伤中HIF-1α及VEGF表达的影响

Effect of hyperbaric oxygen intervention on HIF-1 alpha and VEGF expression in rats with spinal cord secondary injury

目的 观察大鼠脊髓损伤及高压氧干预后不同时期受损脊髓组织内血管内皮生长因子（HIF-1α）及血管内皮生长因子（VEGF）表达的变化,探讨高压氧干预对大鼠急性脊髓损伤后的神经保护机制。方法 将成年SD大鼠80只采用改良Allen’s方法制作脊髓损伤模型,然后将大鼠随机分为2组,损伤组不给予干预措施,干预组辅助以高压氧干预。2组分别于损伤后1,3,7,14 d随机抽取6只大鼠,采用BBB方法评价大鼠后肢运动功能,手术取出受损节段脊髓组织,采用荧光定量PCR法及Western-Blot法检测HIF-1α及VEGF的表达情况。结果 2组大鼠损伤后均表现为双下肢全瘫,BBB评分0~1分;干预组损伤后7,14d BBB评分明显高于损伤组（P均〈0.05）,损伤后3,7,14 d HIF-1αmRNA和蛋白的表达均明显低于损伤组（P均〈0.05）,术后7,14 d VEGF mRNA和蛋白的表达均显著高于损伤组（P均〈0.05）。结论 高压氧干预能够抑制HIF-1α的表达,且不依赖HIF-1α的作用实现VEGF的高表达,延长VEGF高表达的时间,从而发挥神经保护作用。

Objective It is to observe the changes of hypoxia inducing factor - 1 alpha （ HIF - 1 alpha） and VEGF expression in the injuried spinal cord tissue in the rats with spinal cord injury （SCI） before intervention and in different periods after intervention with hyperbaric oxygen, to explore the nerve protective mechanism of hyperbaric oxygen for acute SCI. Methods 80 adult SD rats used to establish SCI models by modified Allen＇ s method, then the models were randomly divided into two groups, the injury group were given no intervention, while the intervention group was treated with hyperbaric oxygen after mod- el establishing. Six rats were randomly selected from each group in 1, 3, 7, 14 days after injury to evaluate hind limbs motor function by BBB method, and their damaged spinal cord segments were taken out by surgery to detect the expression of HIF - 1 alpha and VEGF by fluorescence quantitative polymerase chain reaction （PCR） and Western Blot method. Results All the rats in both group were characterized by double lower limbs panplegia, BBB score of 0 - 1 after injury; the BBB scores in intervention group were significantly higher than that in the injury group in 7, 14 days after injury （ all P 〈 0.05） ; the expression of HIF - lalpha mRNA and protein in intervention group were significantly lower than that in the injury group in 3, 7, 14 days after injury （ all P 〈 0.05 ） , the expression of VEGF mRNA and protein in intervention group were significantly higher than that in the injury group in 7, 14 days after injury （ all P 〈 0.05 ）. Conclusion Hyperbaric oxygen intervention can inhibit the expression of HIF - 1 alpha, and do not rely on HIF - 1 alpha role to realize high expression of VEGF, extend the time of high expression of VEGF, thus to play nerve protective effect.