托吡酯对癫痫持续状态大鼠海马神经元损伤的保护作用

PROTECTIVE EFFECT OF TOPIRAMATE ON NEURONAL INJURY AFTER STATUS EPILEPTICUS IN THE RAT

为探讨托吡酯(topiramate,TPM)对癫痫持续状态(status epilepticus,SE)大鼠海马神经元损伤的保护作用,将大鼠随机分为正常对照组、海人酸(kanic acid,KA)组和TPM预处理组,观察海马神经元超微结构和bcl-2表达的变化。先将TPM组大鼠用TPM预处理,然后采用KA(10mg/kg)腹膜腔注射制作SE模型,在痫性发作终止后6、24和48h取海马进行研究。结果显示:KA组神经元呈凋亡特征;TPM组神经元结构大致正常,但出现核仁边聚和细胞器增多现象,亦观察到少量凋亡神经元。KA组于SE后6h观察到bcl-2表达增高,与对照组相比差异显著,(P<0.05);24h时开始减弱,48h仅有微弱表达;TPM组在24h时bcl-2呈强表达(P<0.001),并持续至48h。以上结果提示:托吡酯预处理能减轻癫痫大鼠神经元的损伤,其机制可能与上调bcl-2的表达有关。

To observe the protective effect of topiramate （TPM） on the hippocampal neurons after status epileptieus （SE） in the rats, 42 SD rats were randomly divided into three groups ： control group, kanie acid （KA） group and TPM group. Then we observed the changes of neuronal ultrastrueture and bcl-2 expression. After pretreated with TPM, the TPM group employed intraperitoneal administration of KA （ 10 mg/kg） to make SE models. The hippocampus was taken out 6, 24 and 48 h after SE. The results were as follows： the neurons of KA group showed characteristic of apoptosis, and those in TPM group were approximately normal, but we could see margination of nueleole and increment of both Golgi body and lysosome. A few apoptotie neurons could also be seen. In KA group, the expression of bel-2 increased 6 h after SE, siguifieantly different with the control group （ P 〈 0.05 ）. It began to decrease at 24 h, and only weak expression could be detected at 48 h. As for TPM group, remarkable expression of bcl-2 could be seen （P 〈0. 001 ） and it lasted to 48 h. These results suggest that pretreatment with TPM could reduce the neuronal injury of epileptic rats, this might be related to the up-regulation of bcl-2 expression.