Rahbar-Roshandel Nahid, Razavi Lili, Tavakoli-Far Bahareh, Mahmoudian Massoud
Razi Institute of Drug Research, Iran University of Medical Science, Tehran, Iran.
Pathophysiology. 2008 Dec;15(4):227-31. doi: 10.1016/j.pathophys.2008.09.002. Epub 2008 Oct 21.
The protective effect of two new L-type calcium-channel blockers, mebudipine and dibudipine on neurotoxic effects induced by glutamate and oxygen-glucose deprivation (OGD) in PC12 cells was investigated. PC12 cells were intoxicated with two different methods. First, the cells were incubated with glutamate (10muM/L), glutamate and mebudipine (10muM/L), dibudipine (10muM/L) or nimodipine (10muM/L), on three different treatment schedules (concurrently, pre-3h and pre-24h). In the second method PC12 cells were exposed to in vitro oxygen-glucose deprivation for 30min and 60min alone or with the drugs in the same time schedules described above. Cellular viability was assessed by MTT assay. Glutamate-induced cell death and OGD-induced cell injury were attenuated significantly by mebudipine, dibudipine in comparison with nimodipine in all three different treatment schedules. Application of MK801 (10muM/L), an antagonist of NMDA glutamate receptors inhibited PC12 cell death in both methods. Our study suggests that mebudipine and dibudipine, like nimodipine, may have protective effects against glutamate and oxygen-glucose deprivation-induced neurotoxicity.
研究了两种新型L型钙通道阻滞剂美布地平和地布地平对PC12细胞中谷氨酸和氧糖剥夺（OGD）诱导的神经毒性作用的保护作用。PC12细胞用两种不同方法进行处理。首先，将细胞与谷氨酸（10μM/L）、谷氨酸和美布地平（10μM/L）、地布地平（10μM/L）或尼莫地平（10μM/L）一起孵育，采用三种不同的处理方案（同时、提前3小时和提前24小时）。在第二种方法中，PC12细胞单独或与上述相同时间方案的药物一起进行30分钟和60分钟的体外氧糖剥夺。通过MTT法评估细胞活力。在所有三种不同处理方案中，与尼莫地平相比，美布地平和地布地平显著减轻了谷氨酸诱导的细胞死亡和OGD诱导的细胞损伤。应用MK801（10μM/L），一种NMDA谷氨酸受体拮抗剂，在两种方法中均抑制了PC12细胞死亡。我们的研究表明，美布地平和地布地平与尼莫地平一样，可能对谷氨酸和氧糖剥夺诱导的神经毒性具有保护作用。
