不同钙离子通道阻滞剂对大鼠脑片皮层扩散性抑制的影响  

THE EFFECT OF DIFFERENT CALCIUM ION BLOCKING CHANNELS ON CORTICAL SPREADING DEPRESSION IN RAT NEOCORTICAL SLICE MODEL IN VITRO

作　　者：季燕[1,2] 万琪[1] 沈飞飞[1] 王静[1] 

机构地区：[1]南京医科大学第一附属医院神经内科,南京210029 [2]南通市第三人民医院神经内科,南通226200

出　　处：《中国疼痛医学杂志》2010年第5期289-292,共4页Chinese Journal of Pain Medicine

摘　　要：目的：利用KCl化学刺激方法在大鼠离体脑片上诱导皮层扩散性抑制（CSD）,并以已知有效抑制药物N-甲基-D-天冬氨酸（NMDA）受体拮抗剂AP-5及σ1受体激动剂dextromethorphan（DM）作为参照,观察钙离子通道阻滞剂在皮层扩散性抑制中的影响。方法：采用6-7周龄的雄性SD大鼠,取大鼠离体脑片做细胞外记录,用2 mol/L KCl局部喷射的方法诱导皮层扩散性抑制,并在电流钳模式下描记CSD的电压和波幅变化,药物干预组则是在灌流液中加入药物,直接观察CSD的变化。所有实验结果均以振幅的平均值±标准误表示,多组间的数据两两比较使用秩和检验。结果：（1）用所建立的电生理学方法记录到的CSD,为细胞外慢电位,峰值30 mV,时长1~2min;（2）抑制药物DM、AP-5干预组与对照组相比差别具有统计学意义（P〈0.01）,盐酸氟桂利嗪组、尼莫地平组与对照组相比差别亦具有统计学意义,同时盐酸氟桂利嗪组与DM、AP-5组相比差别无统计学意义（P〉0.05）,尼莫地平组则与DM、AP-5相比差别具有统计学意义,尼莫地平对CSD的抑制作用不如抑制药物。结论：（1）采用KCl刺激的方法能在大鼠皮层离体脑片上稳定地诱导皮层扩散性抑制;（2）与已知阻断药物相比,T/N型钙离子通道阻滞剂盐酸氟桂利嗪对皮层扩散性抑制有明显的抑制作用,而L型钙离子通道阻滞剂尼莫地平的抑制作用则不明显。Objective： A protocol was performed for inducing cortical spreading depression（CSD） on rat neocortical slices in vitro,and to investigate calcium channel blockers on blocking CSD episodes.Methods： The brain neocortical slices were prepared from male SD rats between 6 and 7 weeks age.Local application of KCl was used to elicit CSD events on the slice recorded by micropipette electrode.This in vitro model was validated by the inhibition of CSD episodes by the NMDA receptor antagonist AP-5 and σ1 receptored agonists Dextromethorphan（DM）,the reference CSD blockers.We investigated whether CSD inhibition in vitro by flunarizine hydrochloride and nimodipine reflects an involvement of calcium channel in CSD events.Results： Application of KCl induced CSD events,recorded by electrophysiology method as slow extracellular DC transients,the peak amplitude was 30 mV,the duration up to 2 min,DM and AP-5 have obviously inhibitory action to CSD,flunarizine hydrochloride has inhibitory action to CSD.Local application of artificial cerebro-spinal fluid was used to elicit CSD events,there is no CSD turn up.Conclusion： T/N type Calcium channels blockers flunarizine hydrochloride inhibit generation and progation of spreading depression in the rat neocortical slice model in vitro.

关 键 词：皮层扩散性抑制(CSD) 钙离子通道 偏头痛先兆 

分 类 号：R965[医药卫生—药理学]