N-methyl-D-aspartate受体阻断剂MK801对离体海马脑片CA1区锥体细胞缺氧期间电生理的影响

The effects of the blocker of the N-methyl-D-aspartate receptor MK801 on the electrophysiological changes of CA1 pyramidal cells during hypoxia in isolated hippocampal slices of rats

目的 应用细胞内记录技术 ,研究 N- methyl- D- aspartate(NMDA)受体阻断剂 MK80 1对离体海马脑片 CA1区锥体细胞缺氧期间电生理的影响。方法 成年雄性 SD大鼠海马脑片随机分为单纯缺氧组 (Con组 ,n=1 0 )和 MK80 1组 (M组 ,n=1 0 )。Con组海马脑片给予 1 0分钟缺氧 ;而 M组的海马脑片在缺氧前 1 0分钟及 1 0分钟的缺氧期间分别应用 1 0 0 μmol/ L 的 MK80 1。所有脑片均给予 6 0分钟的复氧。应用细胞内记录技术记录海马 CA1区神经元缓慢去极化及快速去极化的时间、快速去极化的幅度。在复氧末 ,应用细胞内注入电流及经 Schaffer通路刺激 ,观察神经元对刺激的反应。结果 Con组海马 CA1区锥体神经元缓慢去极化速率为 (0 .2 2± 0 .0 5 ) m V/ s,显著高于 M组的 (0 .0 8± 0 .0 3) m V/ s (P<0 .0 5 ) ;NMDA受体阻断剂 MK80 1可以显著延迟神经元的快速去极化的时间 ,M组神经元的快速去极化时间为 (5 37± 1 39) s,显著高于 Con组的 (2 6 1± 2 6 ) s (P<0 .0 5 ) ;M组 CA1区神经元的快速去极化幅度为 (4± 1 3) m V,显著小于 Con组的 (5 3± 7) m V(P<0 .0 5 )。在复氧末 ,M组的 1 0例神经元中 ,9例神经元恢复对刺激的反应。结论 NMDA受体阻断剂可显著减轻神经元的缺氧性损伤 ,促进复氧后神经元功?

Objective To investigate the effects of the blocker of the N methyl D aspartate (NMDA) receptor MK801 on the electrophysiological changes of CA1 pyramidal cells during hypoxia in isolated hippocampal slices of rats with intracellular recording techniques. Methods The hippocampal slices from adult male rats were randomly divided into Con group (Con group, n =10) and MK801 group (M group, n =10). The slices in Con group subjected to 10min of hypoxia with the artificial cerebrospinal fluid (ACSF) which were saturated with 95%N 2+5%CO 2, and the slices in M group were treated with 100μmol/L MK801 for 10min before and during 10min of hypoxia. All slices in each group had 10min of hypoxia and 60min of re oxygenation. The rate of slow depolarization, the time to rapid depolarization and the amplitude of rapid depolarization were measured,and the neuronal response to the intracellular current injection and Schaffer collateral stimulation were recorded at the end of re oxygenation. Results The rate of slow depolarization and the amplitude of rapid depolarization of hippocampal slices CA1 pyramidal cells were significantly higher than that in M group. MK801 could significantly delay the time to rapid depolarization compared with that in Con group, (537±139)s and (261±26)s respectively ( P <0.05). The number of neurons in M group having response to the intracellular current injection and Schaffer collateral stimulation was markedly more than that in Con group. Conclusion MK801 could protect the hippocampal pyramidal cells in CA1 from the hypoxic injury.