MicroRNA-132拮抗剂对匹罗卡品诱导的幼年大鼠癫癎持续状态的影响

Effect of a microRNA-132 antagonist on pilocarpine-induced status epilepticus in young rats

摘要:

目的 探讨microRNA-132 拮抗剂对氯化锂-匹罗卡品诱导的幼年Sprague-Dawley（SD）大鼠癫癎持续状态（SE）的影响。方法 将3 周龄SD 大鼠分为癫癎模型组、microRNA-132 拮抗剂组和microRNA-132拮抗剂阴性对照组，每组15 只。MicroRNA-132 拮抗剂及其阴性对照预处理在造模前24 h 进行，利用氯化锂-匹罗卡品建立幼年SD 大鼠SE 模型。通过行为学观察各组大鼠SE 发作潜伏期及SE 诱导成功率；Lado 幼鼠癫癎评分观察各组大鼠抽搐发作的严重程度；脑电图监测各组大鼠癫癎样放电的频率及波幅，并统计各组死亡率。结果 在实验各组中，SE 诱导成功率差异无统计学意义（P > 0.05）；与microRNA-132 拮抗剂阴性对照组和癫癎模型组比较，microRNA-132 拮抗剂组大鼠造模以后达到SE 的潜伏期明显延长（P < 0.05），Lado 幼鼠癫癎评分下降（P < 0.05），脑电图显示癎样放电的幅度及频率显著下降（P < 0.05），死亡率稍降低。结论 microRNA-132拮抗剂预处理对氯化锂-匹罗卡品诱导的幼年SD 大鼠SE 发生和发展具有抑制作用，抑制microRNA-132 有可能成为SE 药物治疗的潜在靶点和新方向。

Abstract:

Objective To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats. Methods Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group. Results There was no significant difference in the success rate of induction of SE between the three groups (P > 0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P < 0.05), a significantly lower Lado score of seizure (P < 0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P < 0.05), and a slightly reduced mortality rate. Conclusions The treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.