低氧预适应大鼠皮层缺氧诱导因子-1α的表达及其对细胞凋亡的调控作用

目的探讨低氧预适应对大鼠局灶脑缺血再灌注的脑保护作用及缺氧诱导因子（hypoxic inducible fac-tor,HIF-1）表达对神经细胞凋亡的影响。方法36只大鼠随机分为假手术组、缺血再灌注（I/R）组、低氧预适应（HP＋I/R）组。用线栓法建立大鼠局灶脑缺血-再灌注模型,脑缺血前12h将HP＋I/R组大鼠放在8%低氧舱中完成低氧预适应。分别用免疫组化、原位末端标记法检测HIF-1α的表达和神经元凋亡。结果与假手术组比较,低氧预适应组和缺血再灌注组的HIF-1α表达水平和凋亡细胞阳性数显著升高（P〈0.01,P〈0.01）;低氧预适应组与缺血再灌注组比较,HIF-1α表达水平明显升高（P〈0.01）,细胞凋亡阳性细胞降低（P〈0.01）。结论低氧预适应可能通过显著增加神经元中HIF-1α表达而抑制神经细胞的凋亡,从而发挥脑保护作用。

Hypoxic preconditioning Rat cortex hypoxic inducible factor-1αactivity Regulating and controlling withering to the cell to die acts on

Objective：To study the effect of hypoxic preconditioning in 8% O2for 3 h on the rat brain activity of HIF-1αand nervous cellapoptosisafter rat cerebral ischemia-reperfusion injury.Methods： Rats were subjected to hypoxic preconditioning for 12 h to develop cerebral ischemia-reperfusion model,the middle arteries of rats were occluded for 3 h,and reperfused for 24 h HIF-1α activity level and the apoptotic cell rate were determined in the sham-operated group,the hypoxic preconditioning group and the cerebral ischemia-reperfusion group by using immunofluorescence technique and TUNEL, respectively. Results： The HIE-let activity level and apoptotic cell were significantly higher in the ischemia-reperfusion group and hypoxic preconditioning than those in the sham-operated group（ P 〈 0.01 ,P 〈 0. 05 ）. Compared with hypoxic preconditioning group and the cerebral ischemia-reperfusion group the HIF-1αactivity level were significantly higher in the hypoxic preconditioning group（ P 〈 0. 01）. the apoptotic cell rate increase dramatically（ P 〈 0.01） . Conclusion ： One of the mechanisms of brain protection by hypoxic preconditioning may be due to increase activity level of HIF-1αand decrease of neural cell apoptosis.