蛇床子素对脑缺血/再灌注大鼠海马LTP及氨基酸含量的影响

目的研究蛇床子素对脑缺血/再灌注大鼠海马齿状回突触传递活动及海马内氨基酸含量的影响。方法 SD大鼠随机分为正常组、假手术组、模型组、蛇床子素组(25.0、12.5 mg.kg-1)和尼莫地平组(1.0 mg.kg-1),腔内线栓法制作右侧大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,缺血后2 h再灌。采用2,3,5-氯化三苯基四氮唑(TTC)染色法记录大鼠脑梗死体积、Morris水迷宫法观察大鼠空间学习记忆能力、电生理学方法记录中枢突触传递长时程增强(long-term potentiation,LTP)现象、高效液相色谱法记录大鼠海马内氨基酸含量的变化。结果蛇床子素(25.0、12.5 mg.kg-1,ip)可减少大鼠脑梗死体积,剂量依赖性地缩短大鼠寻找站台的时间,增强大鼠海马齿状回高频刺激(high frequency stimulation,HFS)诱导的LTP,降低再灌后72 h内海马内谷氨酸含量,蛇床子素(25.0 mg.kg-1)对于γ-氨基丁酸产生先降低后升高的调节作用,与尼莫地平组作用结果一致。结论蛇床子素改善学习记忆障碍、增强脑缺血/再灌注大鼠海马齿状回HFS诱导的LTP的作用,与调节海马内谷氨酸、γ-氨基丁酸水平有关。

Effects of osthole on LTP and contents of amino acid in hippocampus of cerebral ischemia-reperfusion rats

Aim To observe the effects of osthole on synaptic transmission activities and contents of amino acid in hippocampus of cerebral ischemia-reperfusion rats.Methods SD rats were randomly divided into normal group,sham-operated group,model group,osthole groups(25.0,12.5 mg·kg-1) and nimodipine group(1.0 mg·kg-1).Rat model of middle cerebral artery occlusion(MCAO) was copied and given reperfusion after 2 h.The infarct volume was shown with 2,3,5-triphenyl tetrazolium chloride(TTC) staining.The spatial learning and memory ability of rats was measured by Morris water maze.Electrophysiological recordings were conducted to detect the effects of osthole on phenomena of synaptic transmission long-term potentiation(LTP)in dentate gyrus(DG) of hippocampus.The contents of amino acids in hippocampus at different time after reperfusion were detected by high performance liquid chromatography(HPLC).Results The infarct volume in osthole group(25.0,12.5 mg·kg-1) was lower than that in model group(P<0.05).Osthole dose-dependently shortened the time of seeking platform and significantly improved the LTP induced by high frequency stimulation(HFS) in the DG of hippocampus.The content of Glu in osthole groups(25.0,12.5 mg·kg-1) was significantly lower than that in model group(P<0.05).Compared with model group,the content of GABA was decreased in osthole groups(25.0,12.5 mg·kg-1) only at 1h after reperfusion,while at 72 h after reperfusion osthole(25.0 mg·kg-1) increased the content of GABA(P<0.05).This result of first decrease and then increase also appeared in nimodipine group.Conclusion Osthole can improve learning and memory impairment and enhance hippocampal LTP in cerebral ischemia-reperfusion rats,which is related to the regulation to Glu and GABA levels.