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作 者:郭锐 秦卫帅 张双勇 张淑玲 GUO Rui;QIN Wei-shuai;ZHANG Shuang-yong;ZHANG Shu-ling(Department of Encephalopathy,Zhengzhou Chinese Medicine Hospital,Zhengzhou 450007;Department of Neurology,Zhengzhou People’s Hospital,Zhengzhou 450003,China)
机构地区:[1]郑州市中医院脑病一科,河南郑州450007 [2]郑州市人民医院神经内科,河南郑州450003
出 处:《中国应用生理学杂志》2020年第5期444-448,共5页Chinese Journal of Applied Physiology
基 金:河南省医学科技攻关计划项目(2018020821)。
摘 要:目的:观察甘麦大枣汤对抑郁模型大鼠行为学及单胺递质的影响,并从突触结构及结构蛋白MAP-2与GAP-43表达改变探讨其潜在作用机制。方法:60只SD大鼠随机分为5组:正常对照组、模型组、氟西汀组(10.8 mg/kg)、甘麦大枣汤高、低剂量组(9.72、4.86 g/kg),每组12只。除对照组外,其余各组大鼠均采用慢性不可预见性温和应激(CUMS)建立抑郁模型,并于造模同时给药组灌胃给药,连续21 d。采用糖水消耗实验和旷场测试评价大鼠抑郁样行为,ELISA法检测海马单胺递质5-HT、NE含量,Golgi染色观察神经元突触损伤情况,免疫组化法和Western blot法检测海马突触结构蛋白MAP-2和GAP-43的表达。结果:与对照组比较,抑郁模型大鼠糖水偏好度及自主活动评分均显著下降(P<0.01),海马5-HT、NE含量显著下降(P<0.01),树突棘缺失明显,同时MAP-2和GAP-43表达均显著下调(P<0.01);甘麦大枣汤干预后,模型大鼠抑郁样行为明显缓解(P<0.01),5-HT、NE含量显著升高(P<0.05),树突棘密度、长度及分枝增加,MAP-2和GAP-43表达显著回升(P<0.01)。结论:甘麦大枣汤能改善抑郁模型大鼠的抑郁样行为,升高海马单胺递质含量,其作用可能与上调突触结构蛋白、缓解神经元突触损伤有关。Objective:To investigate the effects of Ganmai Dazao Tang on behavior and monoamine neurotransmitters in rats with depression,and to explore its potential mechanism from synaptic structure.Methods:Sixty SD rats were randomly divided into 5 groups:normal control group,model group,fluoxetine group(10.8 mg/kg),Ganmai Dazao Tang high and low dose group(9.72,4.86 g/kg),12 rats in each group.Except the control group,the rats in the other groups were all chronically unpredictable mild stress(CUMS)to establish a depression model,and were treated by intragastric administration for 21 days.The depression-like behaviors of rats were evaluated by sucrose consumption test and open field test.The contents of serotonin(5-HT)and norepinephrine(NE)in hippocampus were detected by ELISA.The synaptic damage of neurons was observed by Golgi staining.The synaptic structure protein expression levels of MAP-2 and GAP-43 of hippocampus were detected by Immunohistochemistry and Western blot.Results:Compared with control group,the sucrose preference and autonomic activity scores of the depression model rats were decreased significantly(P<0.01),the levels of 5-HT and NE in hippocampus were decreased significantly(P<0.01),and the dendritic spines were absent,and the expressions of MAP-2 and GAP-43 were down-regulated significantly(P<0.01).After treated with Ganmai Dazao Tang,the depression-like behavior of the model rats was significantly relieved(P<0.01),and the levels of 5-HT and NE were increased(P<0.05).Dendritic spine density,length and branching were increased,the expressions of MAP-2 and GAP-43 were increased(P<0.01).Conclusion:Ganmai Dazao Tang can improve the depression-like behavior of depression model rats and increase the monoamine neurotransmitter content in hippocampus,which may be related to up-regulation of synaptic structural proteins and relief of synaptic damage in neurons.
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