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作 者:喻欣[1] 郭莲军[1] 艾永循[2] 徐旭林[1] 何治[1] 宗贤刚[1]
机构地区:[1]华中科技大学同济医学院药理系,湖北武汉430030 [2]江汉大学医学与生命科学学院药理学教研室,湖北武汉430056
出 处:《中国药理学通报》2007年第4期488-492,共5页Chinese Pharmacological Bulletin
基 金:国家自然科学基金面上项目资助课题(No30371639)
摘 要:目的探讨氯化铯(CsCl)一种非选择性的超极化激活-环核苷酸门控的阳离子通道(HCN通道)阻断剂对小鼠空间学习记忆的影响及其作用的机制。方法在小鼠脑缺血/再灌模型上,连续2wk给予CsCl(200、400mg·kg-1,ig),用Morris水迷宫实验方法检测小鼠空间学习记忆成绩,实验结束后动物处死取脑测定海马组织MDA的含量,SOD、tNOS和iNOS的活性。采用离体海马脑片培养,用高效液相荧光检测方法测定CsCl(0.2,2,20mmol.L-1)对脑片培养液中谷氨酸、甘氨酸和牛磺酸释放的影响。结果与缺血/再灌组相比,CsCl组小鼠的游泳距离延长(P<0.05),海马组织MDA的含量,SOD、tNOS和iNOS的活性无明显改变.在离体海马脑片培养实验,CsCl可剂量依赖性抑制谷氨酸的释放(P<0.05);对其它氨基酸的释放没有影响。结论提示CsCl可损伤小鼠的空间学习记忆,该作用可能与其抑制海马谷氨酸的释放有关。Aim To explore the effect of cesium chloride (CsCl) which a non-specific hyperpolarization-activated and cyclic nucleotide-gated cation channels ( HCN channels) blocker on spacial learning and memory in mouse and the mechanism of action. Methods In ischaemia -reperfusion model of mice, CsCl was given intragastrically in dose of 200 or 400 mg·kg^-1 per day for 2 weeks. Then spacial learning and memory was tested in Morris water maze and the content of MDA, activities of SOD, tNOS and iNOS in hippocampus were detected by using biochemistry methods. And Glutamate, glycine and taurine in culture medium were examined after hippocampus slice were incubated with cesium chloride (0. 2, 2, 20 mmol· L^-1, respectively). Results After mice were treated with CsCl, swimming distance to platform was longer, while content of MDA, activities of SOD, tNOS and iNOS in hippocampus had no changes, when they were compared with ischemia-reperfusion mice. In hippocampus slices of mouse, CsC1 caused a dose-dependent inhibition of glutamates release, and did not alter release of glycine and tanrine from hippocampus slices. Conclusion It suggests that CsCl could worsen spacial learning and memory of mouse and inhibit the release of glutamates from hippocampus which is the possible mechanism of its effect.
关 键 词:氯化铯 超极化激活-环核苷酸门控的阳离子通道 学习和记忆 氨基酸
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