姜黄素通过抑制外伤性癫痫鼠脑组织中mTORC1的表达发挥抗癫痫效应  

Antiepileptic effect of curcumin by inhibition of m TORC1 activity in brain of posttraumatic epilepsy rats

作　　者：陆波[1] 谢延风[1] 石全红[1] 但炜[1] 詹彦[1] 潘凉泽 胡铁弋[1] 

机构地区：[1]重庆医科大学附属第一医院神经外科,重庆400016

出　　处：《第三军医大学学报》2015年第5期414-419,共6页Journal of Third Military Medical University

基　　金：国家临床重点专科建设项目(财社[2011]170号)~~

摘　　要：目的探讨姜黄素在外伤性癫痫鼠中的抗癫痫效应及对哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin,m TOR complex 1,m TORC1))表达的影响。方法 120只SD雄性大鼠按抽签法随机分为对照组、模型组和干预组,每组40只。模型组与干预组构建大鼠皮质铁离子注射癫痫模型,对照组予以生理盐水注射,干预组于造模前1 h腹腔注射姜黄素,连续14 d。各实验组于造模后6、24 h、3、7、14 d时间点进行相应实验。观察大鼠癫痫发作情况,记录大鼠皮层脑电图特点,透射电镜观察注射侧皮层神经元,Western blot检测大鼠注射侧皮层m TORC1蛋白的表达及其磷酸化程度(p-m TORC1),免疫组化法检测p-m TORC1蛋白在大鼠注射侧皮层中的表达。结果对照组未见癫痫发作,干预组较模型组癫痫发作次数明显减少(P<0.05),发作程度明显减轻(P<0.05);脑电图提示干预组脑电波波幅及癫痫波次数较模型组明显减低(P<0.05);电镜见模型组大鼠神经元变性、死亡等改变,干预组大鼠神经元亚细胞结构基本正常;Western blot检测结果显示m TORC1蛋白在模型组中各时间点磷酸化激活程度均显著高于对照组(P<0.05),并于术后24 h达到峰值,在干预组中p-m TORC1显著低于模型组(P<0.05);免疫组化结果提示p-m TORC1在对照组中低表达,模型组中显著高于对照组(P<0.05),干预组中p-m TORC1显著低于模型组(P<0.05)。结论在外伤性癫痫大鼠中,姜黄素可能通过抑制m TORC1磷酸化激活而发挥抗癫痫效应。Objective To investigate antiepileptic effect of curcumin and analyze the expression level of mammalian target of rapamycin complex 1（ m TORC1） in post-traumatic epilepsy rats. Methods SD male rats（ n = 120） were randomly divided into 3 groups： a control group（ n = 40）,a model group（ n = 40）,and an intervention group（ n = 40）. The rat models of epilepsy were established by iron injection to the cortex in the model group and the intervention group,and the rats in the control group were treated by intracortical injection of normal saline. The rats in the intervention group received intraperitoneal injection of curcumin at1 h before modeling,and the curcumin was injected for 14 d. The rats in each group were randomly selected at different time points（ 6 and 24 h,and 3,7 and 14 d） after epileptic seizure. Racine scale was used to evaluate the behavioral changes,and cortical electroencephalogram（ EEG） monitoring was performed to record the EEG features. The neurons in the curcumin-injected cortex were observed with transmission electron microscope. Western blotting was applied to detect the expression of m TORC1 protein and its phosphorylation,and phospho-m TORC1（ p-m TORC1） protein expression in the curcumin-injected cortex was detected by immunohistochemical assay. Results Typical seizures and epileptic discharge were observed in the model group and the intervention group. The frequency and degree of epileptic seizures of the rats in the intervention group were lower than those in the model group（ P〈0. 05）,as well as the epileptic discharge and epileptic wave amplitude at each time point（ P〈0. 05）. The cortical neuron degeneration and death appeared in the model group, while the curcumin-treated epileptic rats exhibited normal subcellular structures. The pm TORC1 protein was more highly expressed in the model group at each time point as compared with the control group（ P〈0. 05）,and peaked at 24 h after injection of Fe Cl3. The p-m TORC1 protein expression of the in

关 键 词：姜黄素 哺乳动物雷帕霉素靶蛋白复合物1 外伤性癫痫 三氯化铁 

分 类 号：R-332[医药卫生] R285.5