摘要
目的研究越鞠甘麦大枣汤的抗抑郁样作用并分析其对小鼠海马突触可塑性的影响。方法昆明小鼠随机分为对照组和越鞠甘麦大枣汤组,给药24 h和7天后进行悬尾测试(Tail suspension test,TST)和强迫游泳测试(Forced swimming test,FST)。运用电生理(electrophysiological experiment)技术检测小鼠海马区Schaffe侧枝-CA1的长时程增强(long term potentiation,LTP),利用western blot方法分析海马脑区α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor,AMPAR)和N-甲基-d-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)相关突触蛋白的表达水平。结果给药24 h和7天后,与对照组小鼠相比,越鞠甘麦大枣汤给药组小鼠在TST(P <0.001)和FST(P <0.01)中的不动时间均明显降低,氯胺酮在给药24 h后显示出抗抑郁作用,但到第7天不能降低小鼠不动时间,越鞠甘麦大枣汤显示出更持久的抗抑郁样作用。电生理实验中,越鞠甘麦大枣汤可增强小鼠海马区的LTP(P <0.001)。Western blot结果显示,GluR1、NR2B以及NR1的表达水平在给药后均明显增加(P <0.05)。结论越鞠甘麦大枣汤可能通过增强昆明小鼠海马脑区LTP,以及增加AMPA和NMDA受体相关突触蛋白的表达水平以提高突触传递效能,从而产生抗抑郁样作用。
Objective To research the antidepressant-like effect of Yueju Ganmai Dazao decoction and analyze the effect of Yueju Ganmai Dazao decoction on hippocampal synaptic plasticity in mice. Methods Kunming mice were randomly divided into two groups: control group and Yueju Ganmai Dazao decoction group. 24 h and 7 d later, the Tail suspension test(Tail suspension test,TST) and the Forced swimming test(Forced swimming test,FST) were performed.The long-term potentiated(long term potentiation, LTP) of Schaffe lateral branch-CA1 in hippocampus of mice was detected by electrophysiological experiment. The expression levels of α-amino-3-hydroxy-5-methyl-4-oxazolonic acid receptor(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor,AMPAR) and N-methyl-d-aspartic acid receptor(N-methyl-D-aspartate receptor, NMDAR) related synaptic proteins in hippocampus of mice were analyzed by western blot. Results Compared with the control group, the immobility time of the Yueju Ganmai Dazao decoction group was significantly lower than that of the control group in TST(P < 0.001) and in FST(P < 0.01). The immobility time of mice was significantly lower than the naive mice after ketamine treatment, but could not affected after 7 days. The results of electrophysiological experiments showed that the LTP in hippocampus of mice was increased by Yueju Ganmai Dazao decoction treatment(P < 0.001). And the expressions of GluR1, NR2 B and NR1 were all increased significantly by administration of Yueju Ganmai Dazao decoction. Conclusion Yueju Ganmai Dazao decoction may improve the synaptic transmission efficiency by increasing the LTP and enhancing the expression levels of AMPA receptor-and NMDA receptor-related synaptic proteins in hippocampus of Kunming mice, thus produce an antidepressant-like effect.
作者
周童
张海楼
沈家敏
王薇
薛文达
陈刚
Zhou Tong;Zhang Hailou;Shen Jiamin;Wang Wei;Xue Wenda;Chen Gang(School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Key Laboratory of Integrative Medicine for Brain Diseases,School of Basic Biomedical Science,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of traditional Chinese Medicine,Jinan University,Guangzhou,510632,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2019年第11期2310-2317,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会青年基金项目(No 81603497):基于ChIP-Seq的CREB介导越鞠丸快速抗抑郁作用分子机制研究,负责人:王薇
国家自然科学基金委青年基金项目(No 81803748):VIPR2介导越鞠丸快速抗抑郁机制研究,负责人:薛文达
江苏省教育厅苏省高校自然科学基金面上基金项目(No 18KJB360009):越鞠丸增强海马神经新生产生抗抑郁作用机制研究,负责人:王薇。
