2,6-二异丙基苯酚、人参皂苷Rg-1和氯化锂逆转电休克后嗅球切除抑郁大鼠学习记忆障碍  

2,6-Diisopropylphenol,ginsenoside Rg-1 and lithium protects against the impairment of learning-memory induced by electroconvulsive shock in depressed rats

作　　者：刘超[1] 闵苏[1] 魏珂[1] 刘东[2] 董军[1] 罗洁[1] 黎平[1] 刘小滨[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016 [2]天津医科大学第二医院神经外科,天津300211

出　　处：《中国药理学通报》2012年第8期1125-1130,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上资助项目(No 30972831)

摘　　要：目的观察2,6-二异丙基苯酚与人参皂苷Rg-1和氯化锂对电休克后抑郁模型大鼠学习记忆、海马内谷氨酸浓度和Tau蛋白磷酸化的影响,比较其药理作用机制,为临床治疗提供依据。方法按2×4析因设计设2个干预因素,即ECT干预(2水平:无处置、施行1疗程电休克)和药物干预(4水平:海马CA1区微量注射2,6-二异丙基苯酚、人参皂苷Rg-1、氯化锂,生理盐水)。电休克结束后行Morris水迷宫测认知能力;取海马通过高效液相色谱法测谷氨酸的浓度;免疫印迹法测Tau-5和p-AT8Ser202表达。结果 2,6-二异丙基苯酚、人参皂苷Rg-1和氯化锂可改善电休克后认知障碍;2,6-二异丙基苯酚和人参皂苷Rg-1可减少谷氨酸浓度;2,6-二异丙基苯酚与人参皂苷Rg-1和氯化锂可降低海马中Tau蛋白磷酸化程度。结论 2,6-二异丙基苯酚与人参皂苷Rg-1和氯化锂均可缓解ECT后的Tau蛋白过度磷酸化进而改善电休克后的学习记忆;前两者与降低海马谷氨酸浓度有关。Aim To explore the reverse of 2,6-Diiso- propylphenol, ginsenoside Rg-1, lithium against the impairment of learning-memory and the hyperphosphoylation of protein Tau induced by electroconvulsive shock and the concentration of glutamic acid in the hippocampus in depressed rats, in order to compare the therapeutic effects and mechanisms of three medicines. Methods As the analysis of variance of factorial design set up two intervention factors which were the e- lectroconvulsive shock groups （two levels： no disposition; A course of electroconvulsive shock ） and the drug intervention groups （four levels： Microinjection of 2,6-Diisopropylphenol, ginsenoside Rg-1, lithium and Saline）. Sixty-four adult depression model rats whose olfactory bulbs were removed were randomly divided into eight experimental groups （ n = 8, in each group）. The Morris water maze test was started in order to eval- uate learning-memory. The content of glutamate in the hippocampus of rats was detected by High Performance Liquid Chromatography. The content of protein Tauwhich includes Tau-5 and p-AT8s~~2~z in the hippocam- pus of rats was detected by Western blot. Results 2, 6-Diisopropylphenol, ginsenoside Rg-1 and lithium protected against the impairment of learning-memory induced by electroconvulsive shock in depressed rats. The 2,6-Diisopropylphenol and ginsenoside Rg-1 re- duced the content of glutamate. These three medicines reduced the hyperphosphorylation of protein Tau in the hippocampus of depressed rats. Conclusions 2,6-Dii- sopropylphenol, ginsenoside Rg-1 and lithium can pro- tect against the impairment of learning-memory induced by electroconvulsive shock in depressed rats though reducing the hyperphosphorylation of protein Tau. The first two are not content with the glutamate in the hippocampus.

关 键 词：2 6二异丙基苯酚 人参皂苷RG1 氯化锂 电休克 学习记忆 谷氨酸 TAU蛋白 过度磷酸化 

分 类 号：R332[医药卫生—人体生理学] R322.81[医药卫生—基础医学]