Lee So-Young, Kim Choong-Young, Lee Jung-Jeung, Jung Jung-Gil, Lee Seong-Ryong
Department of Pharmacology, Kyungpook National University, 700-422 Taegu, South Korea.
Brain Res Bull. 2003 Aug 30;61(4):399-406. doi: 10.1016/s0361-9230(03)00139-4.
(-)-Epigallocatechin gallate has a potent antioxidant property and can reduce free radical-induced lipid peroxidation as a green tea polyphenol. In previous study, systemic administration of (-)-epigallocatechin gallate immediately after ischemia has been shown to inhibit the hippocampal neuronal damage in the gerbil model of global ischemia. Polyamines are thought to be important in the generation of brain edema and neuronal cell damage associated with various types of excitatory neurotoxicity. We examined the effects of delayed administration of (-)-epigallocatechin gallate on the changes in polyamine levels and neuronal damage after transient global ischemia in gerbils. To produce transient global ischemia, both common carotid arteries were occluded for 3 min with micro-clips. The gerbils were treated with (-)-epigallocatechin gallate (50 mg/kg, i.p.) at 1 or 3 h after ischemia. The polyamines; putrescine, spermidine, and spermine levels were examined using high performance liquid chromatography in the cerebral cortex and hippocampus 24 h after ischemia. Putrescine levels in the cerebral cortex and hippocampus were increased significantly after ischemia and the delayed administrations of (-)-epigallocatechin gallate (1 or 3 h after ischemia) attenuated the increases. Only minor changes were noted in the spermidine and spermine levels after ischemia. In histology, neuronal injuries in the hippocampal CA1 regions were evaluated quantitatively 5 days after ischemia. (-)-Epigallocatechin gallate administered 1 h or 3 after ischemia significantly reduced hippocampal neuronal damage. The present results show that the delayed administrations of (-)-epigallocatechin gallate inhibit the transient global ischemia-induced increase of putrescine levels in the cerebral cortex and hippocampus. (-)-Epigallocatechin gallate is neuroprotective against neuronal damage even when administered up to 3 h after global ischemia. These findings suggest that (-)-epigallocatechin gallate may be promising in the acute treatment of stroke.
(-)-表没食子儿茶素没食子酸酯作为一种绿茶多酚,具有强大的抗氧化特性,能够减少自由基诱导的脂质过氧化。在先前的研究中,已表明在缺血后立即全身给予(-)-表没食子儿茶素没食子酸酯可抑制沙土鼠全脑缺血模型中的海马神经元损伤。多胺被认为在与各种类型兴奋性神经毒性相关的脑水肿和神经元细胞损伤的发生中起重要作用。我们研究了延迟给予(-)-表没食子儿茶素没食子酸酯对沙土鼠短暂全脑缺血后多胺水平变化和神经元损伤的影响。为产生短暂全脑缺血,用微血管夹夹闭双侧颈总动脉3分钟。沙土鼠在缺血后1小时或3小时接受(-)-表没食子儿茶素没食子酸酯(50毫克/千克,腹腔注射)治疗。在缺血24小时后,使用高效液相色谱法检测大脑皮层和海马中的多胺(腐胺、亚精胺和精胺)水平。缺血后大脑皮层和海马中的腐胺水平显著升高,而延迟给予(-)-表没食子儿茶素没食子酸酯(缺血后1小时或3小时)可减弱这种升高。缺血后亚精胺和精胺水平仅出现轻微变化。在组织学方面,缺血5天后对海马CA1区的神经元损伤进行定量评估。缺血后1小时或3小时给予(-)-表没食子儿茶素没食子酸酯可显著减少海马神经元损伤。目前的结果表明,延迟给予(-)-表没食子儿茶素没食子酸酯可抑制短暂全脑缺血诱导的大脑皮层和海马中腐胺水平的升高。即使在全脑缺血后3小时给予(-)-表没食子儿茶素没食子酸酯,它对神经元损伤也具有神经保护作用。这些发现表明,(-)-表没食子儿茶素没食子酸酯在中风的急性治疗中可能具有前景。