白藜芦醇对大鼠海马CA1区诱发癫痫样放电的影响

目的观察不同浓度白藜芦醇(resveratrol,Res)对癫痫大鼠海马CA1区场电位的影响,为临床研发抗癫痫新药提供理论依据。方法正常大鼠海马脑片灌流γ-氨基丁酸受体拮抗剂bicuculline引起癫痫样活动以及在正常大鼠右侧海马CA3区注射海人藻酸(KA)建立颞叶癫痫(TLE)大鼠模型,应用离体脑片细胞外场电位记录,刺激辐射层Schaffer侧支通路,在海马CA1区锥体细胞层记录群峰电位(PS)的变化。结果正常大鼠海马脑片CA1区锥体细胞记录到的场电位为单个PS,分别灌流含有低、中和高剂量(分别为5、15和50μmol.L-1)Res的ACSF,PS幅度均无明显变化(n=8,P>0.05)。灌流bicuculline(30μmol.L-1)后,记录到的场电位为多个PS的痫样电位,在此基础上灌流低和中剂量的Res,PS幅度和数目没有明显改变(n=8,P>0.05);而灌流高剂量的Res,前4个PS幅度均有明显降低(n=8,P<0.01),PS数目也有明显减少(n=8,P<0.01)。在TLE模型大鼠海马脑片上记录到的场电位也为多个PS的痫样电位,灌流低和中剂量的Res,PS幅度和数目没有明显改变(n=6,P>0.05);灌流高剂量Res,前4个PS幅度均有明显降低(n=6,P<0.01),PS数目也有明显减少(n=6,P<0.01)。结论高剂量的Res能部分抑制大鼠海马CA1区诱发癫痫样放电活动。

Effects of resveratrol on evoked epileptiform discharges in rat hippocampal CA1 region

Aim To investigate the effects of resveratrol with different concentrations on evoked epileptiform discharges in rat hippocampal CA1 region in order to provide a theoretical basis for the clinical development of antiepileptic drugs.Methods The epileptiform activity was induced by perfusing GABAA receptor antagonist,bicuculline,in normal hippocampal slices and the temporal lobe epilepsy(TLE) model of rat was established by injecting kainic acid into the CA3 region of the right hippocampus.The population spike(PS) of CA1 pyramidal cell layer was recorded with extracellular recording in hippocampal slices by electrical stimulating Schaffer collaterals in stratum radiatum.Results The recorded PS was of a single peak in normal hippocampal slices.The amplitude of PS recorded in normal hippocampal slices was not significantly affected by perfusing ACSF with low,middle and high dose(5 μmol·L-1,15 μmol·L-1 and 50 μmol·L-1) of resveratrol,respectively(n=8,P>0.05).The recorded PS was of 4~6 peaks like multiple epileptiform discharges evoked by perfusing bicuculline(30 μmol·L-1).After perfusing low and middle dose of resveratrol,the amplitudes of the first four peaks of PS and the total peak numbers of PS were not significantly affected(n=8,P>0.05).However,after perfusing high dose of resveratrol,the amplitudes of the first four peaks of PS and the total peak numbers of PS were all decreased obviously(n=8,P<0.01).The recorded PS was also of 4~6 peaks like multiple epileptiform discharges in rat TEL model.After perfusing low and middle dose of resveratrol in rat TLE model,the amplitudes of the first four peaks of PS and the total peak numbers of PS were not significantly affected(n=6,P>0.05).However,after perfusing high dose of resveratrol,the amplitudes of the first four peaks of PS and the total peak numbers of PS were all decreased obviously(n=6,P<0.01).Conclusion High dose of resveratrol can partly inhibit evoked epileptiform discharges in rat hippocampal CA1 region.