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目的观察HCN通道特异性阻滞剂ZD7288对大鼠海马CA3区突触传递的影响。方法应用在体电生理细胞外记录技术记录大鼠海马CA3区场电位,用HPLC荧光检测技术测定海马组织氨基酸含量,观察CA3区局部微量给予ZD7288和CsCl后对低频(0·5 Hz)刺激穿通通路(perforant pathway,PP)诱发的海马CA3区群峰电位(population spike,PS)幅度及海马组织氨基酸含量的影响。结果海马CA3区分别注射ZD7288(20,100和200nmol)和CsCl(1,5和10μmol)可引起PS幅度剂量依赖性下降;药物效应于给药后5 min开始,作用维持时间90 min以上。给予ZD7288(100 nmol)大鼠海马组织谷氨酸、天冬氨酸、甘氨酸及γ-氨基丁酸含量显著降低,与生理盐水对照组比较,差异有显著性意义(P<0·01或P<0·05)。结论 ZD7288可显著抑制大鼠穿通纤维—海马CA3区突触传递,并可降低海马组织氨基酸含量。
Objective To observe the effect of HCN channel blocker ZD7288 on synaptic transmission in hippocampal CA3 area of rats. Methods The field potentials of CA3 in the hippocampus were recorded by electrophysiological extracellular recording technique. The content of amino acids in the hippocampus was measured by HPLC fluorescence detection. The local low-frequency (0.5 Hz) stimulation was observed after the local administration of ZD7288 and CsCl in CA3 area (PP) -induced hippocampal CA3 region population spike (PS) amplitude and amino acid content in hippocampus tissue. Results The injection of ZD7288 (20, 100 and 200 nmol) and CsCl (1, 5 and 10 μmol) in the hippocampal CA3 region caused a dose-dependent decrease in PS amplitude. The drug effect started at 5 min after administration and the effect was maintained for more than 90 min. The levels of glutamic acid, aspartic acid, glycine and γ-aminobutyric acid in hippocampus of ZD7288 (100 nmol) rats were significantly decreased compared with those in saline control group (P <0.01 or P <0 · 05). Conclusion ZD7288 can significantly inhibit the synaptic transmission in rat perforation-fibers-hippocampal CA3 region and decrease the content of amino acids in hippocampus tissue.