Protective effects of iptakalim,a novel ATP-sensitive potassium channel opener,on global cerebral ischemia-evoked insult in gerbils
Protective effects of iptakalim,a novel ATP-sensitive potassium channel opener,on global cerebral ischemia-evoked insult in gerbils作者机构：Department of Anatomy Laboratory of Neuropharmacology Histology and Pharmacology Nanjing Medical University Nanjing China Department of Cardiovascular Pharmacology Beijing Institute of Pharmacology and Toxicology Beijing China
出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期：2006年第27卷第6期
页 面：665-672页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床]
基 金：国家自然科学基金 江苏省卫生厅重点项目 江苏省教育厅自然科学基金 国家教育部高等学校博士学科点专项科研基金
主 题：ATP-sensitive potassium channel opener iptakalim global cerebral ischemia neuroprotection excitotoxicity
摘 要：Aim:To investigate the protective role of iptakalim,a novel ATP sensitive potas-sium channel opener,on global cerebral ischemia-evoked insult in gerbils andglutamate-induced PC 12 cell injury.Methods:Global cerebral ischemia was in-duced by occluding the bilateral common carotid arteries in gerbils for 5 min.Theopen field maze and T-maze were employed to investigate the experimental thera-peutic value of iptakalim on ischemic brain insult（n=8）.The pyramidal cells in thehippocampal CA1 regions were counted to assess the protective effects ofiptakalim.Glutamate released from the gerbil hippocampus and PC12 cells weredetermined by HPLC.Intracellular calcium was measured by Fluo-3 AM with ABio-Rad Radiance 2100TM confocal system in conjunction with a Nikon TE300microscope.Astrocyte glutamate uptake measurements were determined by liq-uid scintillation counting.Results:Iptakalim（0.5-4.0 mg/kg per day,ip）couldreduce the high locomotor activity evoked by ischemia and improve global cere-bral ischemia-induced working memory impairments.Histological studies revealedthat iptakalim could increase the survival neuron in the hippocampus CA1 zone ina dose-dependent manner.Moreover,iptakalim could reverse ischemia-evokedincreases of glutamate in the hippocampus of gerbils.In an in vitro study,iptakalimprotected PC12 cells against glutamate-induced excitotoxicity,reduced the[Ca2+]iincreases,and enhanced the glutamate uptake activity of primary culturedastrocytes.Conclusions:Iptakalim plays a key role in preventing global cerebralischemia-evoked insults in gerbils and glutamate-induced PC12 cell injury by anti-excitotoxicity.Iptakalim might be a promising novel candidate for the preventionand/or treatment of stroke.
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