缝隙连接阻断剂对大鼠癫痫后海马涟波振荡能量变化的影响

Effect of gap junction blockers on hippocampal ripple energy expression in rats with status epilepticus

摘要:

目的 探讨缝隙连接阻断剂奎宁（quinine，QUIN）、甘珀酸（carbenoxolone，CBX）对癫痫大鼠海马涟波（ripple）振荡能量变化的影响。 方法 24只大鼠随机分为模型组、丙戊酸（valproate sodium，VPA）组、QUIN组和CBX组（n=6）。建立氯化锂-匹罗卡品（pilocarpine，PILO）癫痫持续状态（status epilepticus，SE）大鼠模型，VPA组、QUIN组和CBX组在注射PILO前3 d，分别给予VPA（抗癫痫一线药物）200 mg/kg灌胃、QUIN 50 mg/kg腹腔注射、CBX 50 mg/kg腹腔注射。脑电图分析各组大鼠造模前后及推注水合氯醛（止痫）前后海马ripple振荡能量改变。 结果 造模前，正常大鼠海马CA1、CA3、齿状回区均可见ripple振荡表达。与建模前1 d比较，注射PILO后10 min，各组ripple平均能量表达逐渐增强，模型组、VPA组和CBX组在止痫前达到最高峰，QUIN组在PILO注射后60 min达到最高峰（P<0.05）。止痫后，3个干预组ripple平均能量恢复至正常水平；模型组在止痫后1 h ripple平均能量恢复至正常水平；且各组均持续正常水平至SE后3 d。ripple最大能量的变化趋势与平均能量类似。 结论 ripple振荡能量改变可以作为癫痫发作早期预警的定量指标；发作间期ripple振荡能量对癫痫的发作并无提示作用；缝隙连接阻断剂可下调癫痫发作期ripple振荡能量。

Abstract:

Objective To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE). Methods A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (n=6 each). A rat model of SE induced by lithium-pilocarpine (PILO) was prepared. The QUIN, VPA, and CBX groups were given intraperitoneal injection of QUIN (50 mg/kg), VPA by gavage (200 mg/kg), and intraperitoneal injection of CBX (50 mg/kg) respectively, at 3 days before PILO injection. Electroencephalography was used to analyze the change in hippocampal ripple energy before and after modeling, as well as before and after chloral hydrate injection to control seizures. Results Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (P<0.05). The QUIN group had the highest expression level of mean ripple energy 60 minutes after PILO injection. The mean ripple energy returned to normal levels in the three intervention groups immediately after chloral hydrate injection, while in the model group, the mean ripple energy returned to normal levels 1 hour after chloral hydrate injection. The mean ripple energy remained normal till to day 3 after SE in the four groups. The changing trend of maximum ripple energy was similar to that of mean ripple energy. Conclusions The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.