托吡酯对癫癎大鼠海马神经元凋亡的保护作用

Protective effect of topiramate on neuronal apoptosis in hippocampus of rats with seizure

目的探讨托吡酯(TPM)对癫疒间发作大鼠海马神经元凋亡的保护作用。方法给予戊四氮(PTZ)致疒间大鼠TPM 80 mg/(kg.d)(大剂量TPM组)、40 mg/(kg.d)(中剂量TPM组)和生理盐水(对照组)灌胃,共14 d。用原位末端标记(TUNEL)方法标记DNA片段,原位检测大鼠海马CA1和CA3区的凋亡神经元。结果各组大鼠海马CA1、CA3区均出现TUNEL阳性细胞。对照组海马CA1、CA3区TUNEL阳性细胞数分别为(35.83±4.58)个和(36.83±3.87)个;中剂量TPM组分别为(31.52±3.43)个和(32.35±4.69)个;大剂量TPM组分别为(23.50±2.81)个和(25.50±3.72)个。大剂量TPM组与对照组比较差异有非常显著性(均P<0.001),与中剂量TPM组比较差异有显著性(均P<0.05);中剂量TPM组与对照组相比差异无显著性(均P>0.05)。结论大剂量TPM对癫疒间发作后的神经元损伤具有一定的保护作用。

Objective To investigate the protective effect of topiramate （TPM） on neuronal apoptosis in rats with acute seizures. Methods We treated the PTZ-induced seizure rats with TPM at 80mg/（ kg·d） （high-dose group） and 40mg/（ kg·d） （ middle-dose group） or physiological saline （ control group） for 2 weeks. Neuronal apoptosis in CA1 and CA3 regions in hippoeampus was identified by terminal deoxynucletidyl transferase-mediated dUTP-biotin in situ nick end labeling （TUNEL） assay. Results Two weeks following seizures, TUNEL-positive neurons were detected in CA1 and CA3 regions each group. The numbers of TUNEL-positive neurons in CA1 and CA3 of control group were 35.83 ± 4. 58 and 36.83 ±3.83, 23.50 ± 2. gl and 25.50 ±3.72 of high-dose TPM group, 31.52 ±3.43 and 32.35 ± 4. 69 of middle-dose TPM group. There was a very significant difference between highdose TPM group and control group （all P 〈 0. 001 ） , and a significant difference between high-dose TPM group and middle-dose group（all P 〈 0. 05）. However, then was no obvious difference between middle-dose TPM group and control group （all P 〉 0.05 ）. Conclusion High dose administration of TPM after experimental status epilepticus may attenuate seizure-induced hippocampal neuronal injury.