托吡酯对纠正癫痫神经递质异常的可行性研究

A feasibility study of topiramate in correcting neurotransmitter abnormalities in epilepsy

摘要:

目的 研究托吡酯对纠正癫痫神经递质异常的可行性，为今后治疗癫痫寻找新的指导方向。方法 将大鼠随机分为空白对照组（注射生理盐水）、戊四氮组（戊四氮诱导）与观察组（戊四氮诱导+托吡酯治疗），每组20只。记录大鼠惊厥的情况。采用免疫组织化学法对大鼠的神经递质[γ-氨基丁酸（GABA）与谷氨酸（Glu）]变化进行记录，同时检测大鼠大脑皮质与海马区的神经递质（GABA和Glu）含量。结果 采用戊四氮对大鼠进行痫性诱导后，戊四氮组大鼠出现明显的痫性症状，相比空白对照组和观察组差异具有统计学意义（P<0.01）。观察组大鼠在神经递质变化、大脑皮质和海马区（GABA和Glu）含量调节上与戊四氮组相比较，差异具有统计学意义（P<0.01）；与空白对照组相比较，差异无统计学意义（P>0.05）。结论 托吡酯对癫痫出现的神经递质异常具有明显的纠正作用，其通过改善大脑GABA与Glu的调节平衡，减少反复同步放电对大脑造成的损伤。

Abstract:

Objective To investigate the feasibility of topiramate in correcting neurotransmitter abnormalities in epilepsy, and to provide a new direction for the treatment of epilepsy in future.Methods Rats were randomly divided into blank control group (injected with normal saline), pentylenetetrazole group (induced by pentylenetetrazole), and observation group (induced by pentylenetetrazole and treated by topiramate), with 20 rats in each group. The condition of convulsion was recorded for all rats. Immunohistochemistry was used to measure the changes in the neurotransmitters γ-aminobutyric acid (GABA) and glutamic acid (Glu) in rats, and the content of GABA and Glu in the cerebral cortex and the hippocampus was also measured.Results After epilepsy was induced by pentylenetetrazole in rats, the pentylenetetrazole group had significantly marked symptoms of epilepsy compared with the blank control group and the observation group (P<0.01). There were significant differences in the changes in neurotransmitters and the content of GABA and Glu in the cerebral cortex and the hippocampus between the observation group and the pentylenetetrazole group (P<0.01), while there were no significant differences between the observation group and the blank control group (P>0.05).Conclusions Topiramate has a significant corrective effect on neurotransmitter abnormalities caused by epilepsy and reduces the brain injury caused by repeated synchronous discharge through improving the balance of GABA and Glu in the brain.