摘要
目的：观察环氧合酶-2（cyclooxygenase-2，COX-2）抑制剂硝基苯-甲磺酸（NS-398）对幼鼠痫样放电的作用及其对海马CA1锥体神经元突触电活动的影响，研究NS-398在幼鼠痫性发作中的作用。方法：用生后第14天龄SD大鼠制作海马组织脑切片，记录其CA1区锥体神经元场电位，以群峰电位（PS）个数和波幅作为指标来评价脑片放电的变化。给脑片用不同浓度青霉素，建立离体海马脑片痂样放电模型，在脑片灌流液中用不同浓度NS-398，观察对PS个数和波幅的影响。全细胞记录模式下，观察NS-398对海马CA1锥体神经元递质释放和突触活动的影响。分别记录自发性兴奋性突触后电流（sEPSC）和自发性抑制性突触后电流（sIPSC），观察NS-398对其波幅和频率的影响。结果：NS-398浓度为10μmol／L时，对青霉素诱发的痼样放电没有多大的抑制效应；当浓度为20gmol／L时，有明显的抑制作用；为30μmol／L时抑制作用很强，明显降低PS的波幅和减少其频率。NS-398能明显抑制致痴大鼠海马锥体神经元sEPSC的频率，但是对其波幅及衰减时间没有明显的影响；同时NS-398能明显增强致痫大鼠海马脑片锥体神经元sIPSC的频率，明显延长sIPSC的衰减时间，对波幅影响不大。结论：COX-2抑制剂NS-398能减少sEPSC的放电和增强sIPSC的抑制功能，导致兴奋性神经递质的释放减少，降低神经元的兴奋性，从而抑制神经元异常放电。
Objective：To explore the mechanism of eyclooxygenase-2（COX-2）inhibitor in immature epileptic rats by observing the effects of COX-2 inhibitor on hippocampal pyramidal neurons in vitro hippocampal tissue epileptiform discharges and the alterations of synaptic activities. Methods： Hippocampal slices were prepared from 2wk-old Sprague-Dawley（SD）rats for whole-cell patch clamp recording. The hippocampal slice epileptic models were induced with dabbling penicillin into the slices. The alterations of the CA1 pyramidal neuron electrophysiological properties in epileptic rats after dabbling different concentrations of COX-2 inhibitor NS -398 into the slices were analyzed with whole cell recording technology. The alteration of synaptic transmission and synaptic activities caused by NS -398 were recorded after induced epileptic discharge. Results： In the penicillin-induced epileptic discharges brain slices, NS-398 reduced the PS amplitude and their frequency with high concentration （30 μmol/L）. NS -398 significantly inhibited the frequency of spontanous excitatory postsynaptic currents（sEPSCs） of the CA1 pyramidal neurons in epileptic rat hippocampal slices, but there Was no obvious impact on the rate of decay time of sEPSCs. Meanwhile NS -398 significantly enhanced the frequency and prolonged the decay time of spontanous inhibitory postsynaptic currents（sIPSCs）, but there was little impact on the current rate. Conelusion： COX-2 inhibitor can inhibit the epileptic discharge in brain slices,reduce the release of sEPSCs and reinforce the release of sIPSCs to reduce the release of excited neurotransmitters, which suggests a potential therapeutic role for COX-2 inhibitors in chronic epilepsy.
出处
《癫痫与神经电生理学杂志》
2010年第4期193-198,203,共7页
Journal of Epileptology and Electroneurophysiology(China)
