α-硫辛酸对戊四氮点燃大鼠认知功能的保护作用及机制探讨  

Protective effect of alpha-lipoic acid on cognitive impairment induced by pentylenetrazole-induced kindling in rats

作　　者：赵冉冉[1,2] 徐晓臣[3] 檀国军[2] 王维平[2] 张文忠[1] 刘吉祥[4] 

机构地区：[1]河北省邯郸市第一医院急诊科,河北邯郸056002 [2]河北医科大学第二医院神经内科,河北石家庄050000 [3]河北省邯郸市第一医院神经内科,河北邯郸056002 [4]河北邯郸市第一医院神经外科,河北邯郸056002

出　　处：《河北医科大学学报》2015年第3期257-260,共4页Journal of Hebei Medical University

基　　金：河北省医学科学研究重点课题计划(20090371);河北省科学技术研究与发展指导计划项目(11276425)

摘　　要：目的观察α-硫辛酸(alpha-lipoic acid,ALA)对戊四氮(pentylenetetrazole,PTZ)点燃大鼠认知功能的保护作用,并探讨其机制。方法选取36只健康成年雄性SD大鼠随机分为对照组、癲痫组和治疗组,每组12只。癫痫组和治疗组给予PTZ隔日腹腔注射建立PTZ点燃模型,治疗组同时给予ALA腹腔注射,利用Morris水迷宫(Morris water maze,MWM)检测动物空间学习、记忆能力,采用分光光度法检测海马组织中丙二醛(malondialdehyde,MDA)和还原性谷胱甘肽(glutathione,GSH),2',7'-二氯荧光素二乙酸酯(2',7'-dichlorodihydrofluorescein diacetate,DCFH-DA)探针检测脑组织中活性氧自由基(reactive oxygen species,ROS)的变化。结果随着水迷宫训练进行,各组大鼠逃避潜伏期呈逐渐下降趋势,但癫痫组逃避潜伏期时间下降幅度最小,治疗组逃避潜伏期下降幅度较癲痫组更明显。癫痫组在目标象限停留时间显著缩短,海马组织中MDA和ROS明显增高,GSH含量明显降低(P<0.05);治疗组与癫痫组相比,目标象限停留时间明显延长,海马组织中ROS和MDA含量明显降低,GSH含量明显升高(P<0.05)。结论氧化应激在癫痫中有非常重要的作用,ALA抗氧化治疗能够减轻脑组织中氧化应激损伤,改善癫痫大鼠的认知功能,为癫痫的治疗提供了新的思路。Objective To explore the protective effect of alpha-lipoic acid（ALA） on cognitive function in an epilepsy model by pentylenetetrazole（PTZ）-kindling and the mechanism.Methods The healthy adult male 36 SD rats were randomly assigned into three groups：control group,PTZ group,and drug therapy group（12 rats,each group）.PTZ and drug therapy groups were injected intraperitoneally with PTZ to establish PTZ-kindling model.ALA was injected intraperitoneally in the drug therapy group.Morris water maze was used to evaluate spacial learning and memory function.Spectrophotometry was used to detect the levels of malondialdehyde and glutathione.2＇,7＇-dichlorodihydrofluoresce in diacetate probe was used to detect the level of reactive oxygen species in the hippocampi of the rats.Results In the Morris water maze,all animals showed a progressive decline in the escape latency with training.The rats in PTZ group exhibited a significant prolongation of escape latency.In PTZ group,the escape latency was significantly prolonged（P0.05） and time spent in the target quadrant was shortened（P0.05）,ROS and MDA significantly increased（P 0.05）,but GSH significantly decreased（P 0.05）.However,administration of ALA significantly improved the performance in MWM,and decreased the contents of ROS and MDA,increased the level of GSH.Conclusion Oxidative stress plays an important role in the pathogenesis of epilepsy,ALA can effectively protect cognitive function and ameliorate oxidative damage,which provides a new way for treating cognitive impairment induced by epilepsy.

关 键 词：癫痫 戊四唑 硫辛酸 认知 

分 类 号：R742.1[医药卫生—神经病学与精神病学]