喹硫平对脑皮质发育不良大鼠癫痫易感性的影响

The effects of quetiapine on the susceptibility to epilepsy in rats with cerebral cortical dysplasia

目的:探讨喹硫平(QUE)对脑皮质发育不良(CD)大鼠的癫痫易感性的影响及作用机制.方法:将SD幼年大鼠分为对照组(control)、脑皮质发育不良组(CD)和喹硫平给药组(CD+QUE).通过钴60(^(60)Co)照射妊娠SD大鼠建立CD模型,CD+QUE组大鼠通过腹腔注射QUE进行治疗.比较各组大鼠的体质量和脑质量,通过表型观察各组大鼠对戊四氮诱导癫痫发作的易感性,利用免疫组织化学染色与Western Blot检测大鼠皮层和胼胝体髓鞘碱性蛋白(MBP)的表达.结果:CD+QUE组大鼠的脑质量和体重低于control组,但明显高于CD组;在戊四氮诱导癫痫发作研究中,诱发强直-阵挛发作所需的戊四氮剂量,CD+QUE组高于CD组,且CD+QUE组诱导全面强直-阵挛发作的平均潜伏期延长,最小发作与全面发作之间的时间间隔延长;免疫组织化学染色及Western Blot分析显示,CD+QUE组与CD组相比,大脑皮质和胼胝体的髓鞘明显增多.结论:喹硫平可促进皮质发育不良大鼠的髓鞘发育,进而降低对戊四氮诱导癫痫的易感性.提示喹硫平可能通过改善髓鞘的损伤、促进其髓鞘发育,降低其癫痫易感性,从而改善CD症状.

Objective:To explore the effect of quetiapine(QUE)on the susceptibility to epilepsy in rats with cerebral cortical dysplasia(CD)and its mechanism.Methods:The SD rats were divided into control group,cortical dysplasia group and quetiapine administration group.The CD model was established by irradiating pregnant rats with cobalt 60(Co).CD+QUE group rats were treated by intraperitoneal injection of QUE.The body weight and brain weight of rats were measured and compared.The seizures pentylenetetrazol-induced were observed to evaluate the susceptibility to epilepsy in the rats.Immunohistochemical staining and Western Blot were used to observe the expression of myelin in each group.Results:The brain weight and body weight of the quetiapine-administered rats were lower than those of the control group,but significantly higher than those of the CD group.The dose of pentylenetetrazol required to induce tonic-clonic seizures was higher in the quetiapine-administered group than in the CD group.In the quetiapine-administered group,the mean incubation period of general tonic-clonic seizures was prolonged,and the time interval between the smallest seizure and the general seizure was prolonged.Immunohistochemical staining and Western Blot analysis showed that compared with the CD group,the myelin in the cerebral cortex and corpus callosum was significantly increased in the quetiapine administration group.Conclusion:Quetiapine may promote the development of myelin in rats with cortical dysplasia,thereby reducing the susceptibility to epilepsy induced by pentylenetetrazol.It is suggested that quetiapine may improve the symptoms of CD by alleviating the damage of myelin,promoting the development of myelin,and reducing the susceptibility to epilepsy.