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氯通道阻断剂对NMDA诱导培养海马神经元凋亡的保护作用
http://www.100md.com 《南方医科大学学报》 2006年第2期
氯通道阻断剂,,氯通道阻断剂;NMDA;海马神经元;凋亡;大鼠摘要,NMDA受体的激活在缺血性脑损伤神经元死亡中起重要作用。本研究利用NMDA诱导大鼠培养海马神经元凋亡,模拟建立缺血性脑损伤的细
     关键词:氯通道阻断剂;NMDA;海马神经元;凋亡;大鼠

    摘要: NMDA受体的激活在缺血性脑损伤神经元死亡中起重要作用。本研究利用NMDA诱导大鼠培养海马神经元凋亡,模拟建立缺血性脑损伤的细胞模型,观察了3种氯通道阻断剂对神经元凋亡的保护作用。离体培养12 d的SD大鼠海马神经元,在NMDA处理前和处理后使用氯通道阻断剂,对神经元的存活率影响不同,仅NMDA处理前给药才有保护作用。SITS对NMDA诱导神经元凋亡的保护作用最强并有浓度依赖性,DIDS次之,NPPB没有明显的保护作用。 结果表明,SITS和DIDS可阻断NMDA的毒性效应,作用机制可能与NMDA的效应和氯通道活动均被阻断有关。

    Neuroprotection of chloride channel blockers against NMDA-induced apoptosis of cultured rat hippocampal neurons

    CHANG Quan-zhong, HU De-hui, CHEN Ming, WANG Ying, GAO Tian-ming

    Department of Neurobiology, Southern Medical University, Guangzhou 510515, China

    Abstract: Activation of N-methyl-d-aspartic acid (NMDA) receptor plays an important role in neuronal apoptosis induced by cerebral ischemia but the underlying mechanisms are still unclear. The present study examined the neuroprotection of three chloride blockers in an in vitro cell model of cerebral ischemia established by treatment of cultured rat hippocampal neurons with NMDA. Hoechst 33258 staining and MTT assay were used to detect neuronal apoptosis and cell viability, respectively. The neuroprotective effects of chloride channel blockers on the cell viability and neuronal apoptosis were only observed when the blockers were applied before NMDA exposure. In comparison with DIDS, SITS showed more potent protective effect in a dose-dependence manner when, whereas NPPB showed no significant neuroprotective effect. The results demonstrate that pretreatment with both SITS and DIDS have protective effect against neuronal apoptosis, which is achieved by blocking both NMDA receptor and chloride channel. ......

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