生酸枣仁拮抗条件性恐惧致焦虑大鼠作用及作用机制研究  

Antagonistic Effect and Mechanism of Raw Zizyphi Spinosae Semenon on Anxiety Induced by Conditional Fear in Rats

作　　者：金阳[1] 朱海玲 宋丹彤 王艳艳[1] 吕涵 李廷利[1] 黄莉莉[1] JIN Yang;ZHU Hai-ling;SONG Dan-tong;WANG Yang-yang;LYU Han;LI Ting-li;HUANG Li-li(Heilongjiang University of Chinese Medicine,Harbin Heilongjiang 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040

出　　处：《时珍国医国药》2024年第2期265-270,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82003974);黑龙江省自然科学基金(LH2022H086);黑龙江省博士后科研启动项目(LBH-Q19057)。

摘　　要：目的探讨生酸枣仁拮抗条件性恐惧致焦虑大鼠的作用和作用机制。方法SD大鼠随机分为4组:空白组、模型组、地西泮组(3.6 mg/kg)和生酸枣仁组(5.0 g/kg)。利用条件性恐惧方法复制焦虑模型,模型复制后,经灌胃途径给药10d。于末次给药1h后,用旷场实验(OFT)和高架十字迷宫实验(EPM)评价条件性恐惧致焦虑大鼠的焦虑样行为;酶联免疫吸附法(ELisa)检测血清中皮质酮(CORT)含量,皮质、海马和杏仁核中CORT、脑源性神经营养因子(BDNF)、5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、谷氨酸(GLU)和γ-氨基丁酸(GABA)含量并计算Glu/GABA的比值。结果在行为学实验中,与空白组相比,模型组大鼠在OFT实验中的跨格次数、中央格运动时间和进入中央格次数均减少(P<0.05或P<0.01);在EPM实验中开/总时间百分比和开/总次数百分比均减少(P<0.01)。与模型组相比,地西泮组大鼠在OFT中跨格次数及中央格运动时间均增加(P<0.01),生酸枣仁组在OFT中各指标均无显著性差异(P>0.05);地西泮组和生酸枣仁组大鼠在EPM中的总入臂次数、开/总时间百分比和开/总次数百分比均增加(P<0.05或P<0.01)。在Elisa法实验中,与空白组相比,模型组皮质、海马与杏仁核中的CORT、Glu的含量和Glu/GABA均增加、GABA的含量均减少(P<0.05或P<0.01),在皮质和海马中BDNF的含量均减少、5-HT、NE和DA的含量均增加(P<0.05或P<0.01),但杏仁核中仅DA的含量增加(P<0.01),BDNF、5-HT及NE的含量减少或增加(P>0.05)。与模型组相比,地西泮组和生酸枣仁组大鼠皮质、海马与杏仁核中的CORT、NE、Glu和GABA的含量均减少、Glu/GABA的比值均增加(P<0.05或P<0.01),皮质和海马中BDNF的含量均增加(P<0.01),皮质中5-HT和DA含量均减少(P<0.01)、但杏仁核中BDNF的含量增加、5-HT的含量减少和海马中DA的含量减少(P>0.05);地西泮组大鼠杏仁核中DA的含量减少(P<0.05),但海马5-HT的含量减少(P>0.05)Objective To investigate the antagonistic effect and mechanism of raw Zizgphi Spinosae semen on anxiety induced by conditioned fear in rats.Methods SD rats were randomly divided into 4 groups:control group,model group,diazepam group(3.6 mg/kg)and sour jujube seed group(5.0 g/kg).The anxiety model was duplicated by the conditional fear method.After replication of the model,the drug was administered by gavage for 10 days.One hour after the last administration,the anxiety-like behavior of the rats with anxiety caused by conditional fear was evaluated by open-field test(OFT)and elevated cross maze test(EPM);The content of cortisol(CORT)in serum,CORT,brain-derived neurotrophic factor(BDNF),5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine(DA),glutamate(GLU)andγ-Aminobutyric acid(GABA)content and calculate the ratio of Glu/GABA.Results In the behavioral experiment,compared with the control group,the rats in the model group had fewer times of crossing the grid,moving time in the central grid and entering the central grid in the OFT experiment(P<0.05 or P<0.01);In the EPM experiment,the percentage of open/total time and the percentage of open/total times decreased(P<0.01).Compared with the model group,the number of cross-grid and central grid movement time of rats in diazepam group increased(P<0.01);The total arm entry times,the percentage of open/total time and the percentage of open/total times in EPM of rats in diazepam group and raw Zizyphi Spinosae group increased(P<0.05 or P<0.01).In the Elisa method experiment,compared with the control group,CORT,Glu content and Glu/GABA content in the cortex,hippocampus and amygdala of the model group increased,GABA content decreased(P<0.05 or P<0.01).Compared with the model group,the contents of CORT,NE,Glu and GABA in the cortex,hippocampus and amygdala of rats in diazepam group and raw Zizyphi Spinosae group decreased,the ratio of Glu/GABA increased(P<0.05 or P<0.01).In diazepam group,the content of DA in amygdala decreased(P<0.05),but the content of 5-HT in hippocampus d

关 键 词：生酸枣仁 焦虑 条件性恐惧 作用机制 

分 类 号：R285.5[医药卫生—中药学]