摘要
目的 :探讨托吡酯 (TPM)对癫痫发作大鼠海马神经元凋亡的影响及其可能的机制。方法 :采用戊四氮致痫模型 ,大鼠癫痫发作后连续给予托吡酯 (80 mg· kg- 1 · d- 1 和 4 0 mg· kg- 1 · d- 1 ) ,共 14 d。以 TU NEL方法标记 DNA片段 ,原位检测海马 CA1和 CA3区的神经细胞凋亡。结果 :各组大鼠海马 CA1、CA3区均出现 TU NEL阳性细胞。对照组海马 CA1、CA3区 TUNEL阳性细胞数分别为 (35 .83± 4 .5 8)个和 (36 .83± 3.87)个 ;4 0 mg· kg- 1 · d- 1 托吡酯组分别为 (31.5 2± 3.4 3)个和 (32 .35± 4 .6 9)个 ;80 mg· kg- 1 · d- 1 托吡酯组为 (2 1.17± 3.0 6 )个和 (2 1.16± 3.87)个。 80 mg· kg- 1 · d- 1 托吡酯组与对照组比较存在极显著差异 (P<0 .0 0 1) ,4 0 mg· kg- 1 · d- 1 托吡酯组与对照组相比无显著差异 (P>0 .0 5 )。结论 :TPM对癫痫发作后神经元凋亡具有一定的保护作用。
Objective: To investigate the effect and mechanism of topiramate on the neuronal apoptosis in rat brain by acute seizures. Methods: The rats were given with topiramate (TPM) at 80mg·kg -1·d -1 or Cabamazipine at 40mg·kg -1·d -1 for 2 weeks. Programmed cell death (Apoptosis) was identified by terminal deoxynucletidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) assay to detect DNA fragmentation. Results: Two weeks following seizures, TUNEL-positive neurons were detected in CA1, CA3 subfields in each group. The number of TUNEL-positive neurons in CA1 and CA3 of control group were (35.83±4.58), (36.83±3.83) respectively; Those of 80mg·kg -1·d -1 TPM group were (21.17±3.06),(21.16±3.87)respectively and of 40mg·kg -1·d -1 group were (31.52 ±3.43), (32.35 ±4.69) respectively. Administration of topiramate significantly reduced hippocampal neuronal damage. However, no differences in histological study of TUNEL-positive neurons between 40mg·kg -1·d -1 TPM and control groups was found. Conclusions: Administration of TPM after experimental status epilepticus can attenuate seizure-induced hippocampal neuronal injury.
出处
《华夏医学》
2004年第6期874-876,共3页
Acta Medicinae Sinica
关键词
癫痫
凋亡
托吡酯
epilepsy
apoptosis
topiramate
