姜黄素通过抑制外伤性癫痫鼠脑组织中p-mTORC1表达发挥抗癫痫效应.docVIP

姜黄素通过抑制外伤性癫痫鼠脑组织中mTORC1表达发挥抗癫痫效应 陆 波，谢延风，石全红，但 炜，詹 彦，潘凉泽，胡铁弋（400016 重庆，重庆医科大学附属第一医院神经外科） [摘要] 目的 探究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, mTOR complex 1，mTORC1))表达的影响。方法 120只SD雄性大鼠随机分为对照组、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 h、24 h、3 d、7d、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mTORC1蛋白的表达及其磷酸化程度（p-mTORC1），免疫组化法检测p-mTORC1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mTORC1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24h达到峰值，在干预组中显著低于模型组(P＜0.05）；免疫组化结果提示p-mTORC1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-mTORC1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mTORC1磷酸化激活而发挥抗癫痫效应。 [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 Curcumin has antiepileptic effect by inhibiting mTORC1 activity in the brain of posttraumatic epilepsy rats Lu Bo Xie Yanfeng Shi Quanghong Dan Wei zhanyan Pang Liangze Hu Tieyi（Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, chongqing 400016,China) [Abstract] objective To investigate the?antiepileptic effect of curcumin and the effect on the expression levels of the mammalian target of rapamycin complex 1 (mTORC1) in the post-traumatic epilepsy rats. Methods 120 SD rats were randomly divided into three groups：control group，model group and intervention group, The rat models of epilepsy were established by iron injection in rat cortices in the latter two groups, and the animals of the control group were administered with an intracortical injection of equal saline. The rats of intervention groups received an intraperitoneal injection of curcumin 1 hour before modeling and received continuous use for 14 days. Rats in each group were randomly selected at each time points(6h，24h，3d，7d，14d)after epileptic seizure.Racine scale was used to evaluate the behavioral changes,Cortical electroencephalogram(EEG) monitoring