Chang Quan-zhong, Hu De-hui, Chen Ming, Wang Ying, Gao Tian-ming
Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2006 Feb;26(2):158-61.
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-dependent manner, 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.
N-甲基-D-天冬氨酸(NMDA)受体的激活在脑缺血诱导的神经元凋亡中起重要作用,但其潜在机制仍不清楚。本研究在通过用NMDA处理培养的大鼠海马神经元建立的脑缺血体外细胞模型中,检测了三种氯离子阻滞剂的神经保护作用。分别使用Hoechst 33258染色和MTT法检测神经元凋亡和细胞活力。仅当在NMDA暴露前应用阻滞剂时,才观察到氯离子通道阻滞剂对细胞活力和神经元凋亡的神经保护作用。与DIDS相比,SITS以剂量依赖方式显示出更强的保护作用,而NPPB未显示出明显的神经保护作用。结果表明,SITS和DIDS预处理均对神经元凋亡具有保护作用,这是通过阻断NMDA受体和氯离子通道实现的。