阿司匹林对匹罗卡品诱导大鼠癫痫持续状态后海马异常神经发生的影响

Effects of aspirin on the aberrant neurogenesis of hippocampus after pilocarpine-induced status epilepticus in rats

目的探讨阿司匹林对匹罗卡品诱导大鼠癫痫持续状态后海马异常神经发生的影响。方法应用氯化锂-匹罗卡品诱导癫痫大鼠模型,将75只雄性SD大鼠随机分为正常对照组、模型组、0 h阿司匹林(20 mg/kg,腹膜腔内注射1次/d)干预组、3 h阿司匹林干预组和24 h阿司匹林干预组(造模终止后干预组以开始干预时间点的不同分为0 h,3 h和24 h三组)。连续给药20 d。癫痫发作后6 d腹腔注射Brd U 50 mg/kg以标记海马新生细胞,间隔12 h,连续给药4次。应用DCX标记新生神经元。结果 (1)Brd U注射后28 d,与正常对照组相比,模型组齿状回Brd U阳性细胞明显增多,模型组Brd U阳性细胞向门区异常迁移;阿司匹林干预组门区Brd U阳性细胞数量较模型组明显降低(P<0.05),而0 h Asp、3 h Asp和24 h Asp组间无明显差异(P>0.05)。(2)癫痫持续状态(SE)后,新生神经元表现出异常迁移模式,形成异位门区基树突和门区异位神经元。阿司匹林干预组异位门区基树突的数量及突起的长度较癫痫组均明显降低(P<0.05),而0 h Asp、3 h Asp和24 h Asp组间差异无统计学意义(P>0.05)。结论阿司匹林可以减少癫痫大鼠新生神经元的异常迁移。

Objective To explore the effect of aspirin on the aberrant neurogenesis in the hippocampus after pilocarpine-induced status epilepticus（ SE）. Methods A total of 75 male SD rats were randomly assigned into control group,epileptic group,and three aspirin groups. The aspirin group was divided into 0 h aspirin group,3 h aspirin group and 24 h aspirin group according to the time of start intervention of aspirin. Lithium and pilocarpine were used to induce epileptic seizures in rats in epileptic group and aspirin group. The rats were intraperitoneally injected with 20 mg/kg aspirin once a day for the subsequent 20 d after the termination of SE. Rats received Brd U（ 50 mg/kg per injection） four times,with 12 h intervals at day 6 after seizures to label newborn cells in the hippocampus. DCX staining was employed to label newborn neurons. Results At day 28 after Brd U injection,the number of Brd U-labeled cells in the DG increased in epileptic group in comparison with control group,and the positive cells abnormally migrated to the hilus. Compared with epileptic group,the number of newborn cells in the hilus was significantly decreased in aspirin groups（ P〈 0. 05）,but there was no statistical difference among 0 h Asp,3 h Asp and 24 h Asp groups（ P〉 0. 05）. After SE,many DCX-positive neurons were found to migrate into the hilus and induced the formation of aberrant hilar basal dendrites and hilar-ectopic newborn neurons. The length and number of dendritic processes reaching into the hilus were decreased in aspirin groups compared with epileptic group（ P〈 0. 05）,but there was no statistical difference among 0 h Asp,3 h Asp and 24 h Asp groups（ P〉 0. 05）. Conclusion Aspirin may reduce the aberrant migration of newborn cells after SE.