低氧预处理减缓缺氧对大鼠海马突触功能抑制及其机制初探

Protection of Hypoxic-Preconditioning Against Anoxic Inhibition of Population Spikes in the Hippocampus Through Decreased Expression of c-fos

目的:探讨低氧预处理对大鼠海马神经元缺氧性神经突触损伤的保护作用及其机制。方法:(1)将成年雄性Wistar大鼠或培养的新生大鼠海马神经元分别随机分为三组:对照组、缺氧组和低氧预处理组。麻醉后分别取海马切片,进行CA3区Schaffer侧支刺激,记录CA1区椎体细胞诱发电位的变化。(2)将新生大鼠海马神经元培养7-11d,分组处理后,用免疫组织化学染色方法检测三组海马神经元c-fos蛋白表达变化并进行光密度分析。结果:经低氧预处理后,可以使海马脑片的群峰电位在缺氧后开始减小、完全消失的时间出现延迟,分别为(4.52±0.99)min和(9.04±1.93)min,与缺氧组比较差异有统计学意义(P<0.05);培养的海马神经元c-fos表达阳性率显著性降低、平均光密度值显著性减少(P<0.05)。结论:低氧预处理可以延缓缺氧对大鼠海马神经突触的抑制作用,这种保护作用可能与神经元c-fos表达减少有关。

Objective：To investigate the effect of hypoxic-preconditioning on anoxic inhibition of population spike of hippocampal slice and c-fos expression in cultured neurons.Methods：Either hippocampal slices or cultured neurons were randomly divided into three groups,which were control group and acute hypoxic groups with or without hypoxic-preconditioning.（1）After hippocampal slices were taken from above three different groups,Schaffer collateral in CA3 area was stimulated,and then the changes of evoked potential in the vertebral cell of CA1 area were recorded.（2）The primary hippocampal neurons after 7-11 days culture were treated by acute hypoxia with or without hypoxic-preconditioning.The expression of cfos induced by anoxia was evaluated by immunocytochemistry and analyzed by the optical density.Results：Treated with hypoxic-preconditioning,the diminished and even abolished time of population spikes of hippocampal slices were significantly increased as（4.52±0.99）min vs（9.04±1.93）min,compared with the hypoxia group（P〈0.05）.The expression of c-fos induced by anoxia in primary cultured hippocampal neurons treated with hypoxic-preconditioning was reduced significantly（P〈0.05）,and the average optical density was significantly decreased（P〈0.05）.Conclusion：Hypoxic-preconditioning may protect against anoxic inhibition on neuronal synapse,which may be likely related to c-fos expression pathway.