Na^+/Ca^(2+)交换抑制剂在大鼠海马缺氧损伤中的作用

ROLE OF Na +/Ca 2+ EXCHANGE BLOCKER IN RAT HIPPOCAMPAL INJURY DURING ANOXIA

本文以大鼠离体海马脑片和分散培养的海马神经元为标本，分别采用微电极记录技术和激光扫描共聚焦显微镜动态监测单个神经元［Ｃａ２＋］ｉ的方法，研究Ｎａ＋／Ｃａ２＋交换抑制剂Ｂｅｎｚａｍｉｌ对缺氧后海马脑片损伤以及海马神经元［Ｃａ２＋］ｉ变化的影响。结果显示，预先用Ｂｅｎｚａｍｉｌ（５０μｍｏｌ）灌流的海马脑片缺氧后ＰＶ持续时间较对照组显著延长，提示其可延缓海马不可逆缺氧损伤的发生；共聚焦测［Ｃａ２＋］ｉ实验进一步发现，急性缺氧可诱导海马神经元［Ｃａ２＋］ｉ迅速升高，而Ｂｅｎｚａｍｉｌ（２０μｍｏｌ）能显著抑制缺氧引起的［Ｃａ２＋］ｉ升高。上述结果表明，抑制神经元Ｎａ＋／Ｃａ２＋交换活动可提高海马脑片抗缺氧能力，其作用机制可能与抑制缺氧所致神经元［Ｃａ２＋］ｉ升高有关，由此推测Ｎａ＋／Ｃａ２＋交换体参于大鼠海马脑区缺氧损伤。

Effects of Na +/Ca 2+ exchange blocker, Benzamil, on rat hippocampal slices and on cultured hippocampal neuronal [Ca 2+ ] i (intracellular free Ca 2+ concentration) during anoxia were investigated by means of microelectrode recording technique and laser scanning confocal microscope respectively. The results showed that the PV sustained time of hippocampal slices pretreated with Benzamil (50μmol) after anoxia was markedly longer than that of control, suggesting that inhibition of Na +/Ca 2+ exchange can delay the irreversible injury to hippocampal cells. Moreover, by using a confocal microscope we found that acute anoxia induced a rapid increase of [Ca 2+ ] i in hippocampal neurons and this could be significantly attenuated by 20μmol Benzamil. All these results indicate that Na +/Ca 2+ exchanger is involved in the anoxic injury to rat hippocampus and it may be one of the major ways leading to the anoxia induced [Ca 2+ ] i increase of hippocampal neurons.