定志小丸和开心丸对CUMS模型大鼠的抗抑郁作用及机制研究  

Antidepressant Effects and Mechanism of Dingzhixiaowan and Kaixinwan on CUMS Model Rats

作　　者：杨黎 刘婉婉[3] 周小江[3] 张兰[1] 董宪喆 刘屏[3] YANG Li;LIU Wanwan;ZHOU Xiaojiang;ZHANG Lan;DONG Xianzhe;LIU Ping(Department of Pharmacy,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;College of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563000,China;Department of Clinical Pharmacology and Pharmacy,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]首都医科大学宣武医院药学部,北京100053 [2]遵义医科大学药学院,贵州遵义563000 [3]中国人民解放军总医院临床药理研究室,北京100853

出　　处：《中国药物警戒》2021年第12期1138-1143,共6页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(81373996,81302909,81673877)。

摘　　要：目的比较《备急千金药方》定志小丸和《医门方》开心丸对慢性不可预知性温和应激抑郁模型(chronic unpredictable mild stress,CUMS)大鼠的影响及可能的作用机制。方法建立CUMS大鼠模型,将大鼠随机分为正常组、模型组、定志小丸组、开心丸组,连续灌胃2周;通过体重、糖水偏嗜度、旷场实验评价两组药物抗抑郁作用,并测定各组大鼠海马和皮层中谷氨酸(glutamic acid,GLU)、γ-氨基丁酸(gama-aminobutyric acid,GABA)及血清下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴递质、IL-1等细胞因子的含量变化,分析定志小丸和开心丸的化学成分差异。结果定志小丸可明显增加CUMS大鼠的体重、糖水偏嗜度和旷场得分,降低大鼠海马和皮层中GLU含量,升高GABA含量,降低HPA轴递质,并调节血清细胞因子的水平。开心丸可升高大鼠海马和皮层中的GABA含量,降低血清细胞因子水平。结论定志小丸具有明显的抗抑郁作用,开心丸在行为学实验中抗抑郁作用不明显。定志小丸的抗抑郁作用可能与调节中枢神经元氨基酸的分泌、逆转HPA轴功能的亢进、降低IL-1等细胞因子的免疫调节有关,组方的抗抑郁作用可能与人参皂苷等主要化学成分的含量密切相关。Objective To compare the effect of Dingzhixiaowan pills recorded in Essential Recipes for Emergent Use Worth One Thousand and Kaixinwan pills recored in Yimenfang on chronic unpredictable mild stress(CUMS)depression model rats and its possible mechanism.Methods A CUMS rat model was established.The rats were randomly divided into the normal group,model group,Dingzhixiaowan group,and Kaixinwan group.The rats in the last two groups were given their respective drug intragastrically for two weeks.The antidepressant effect of the two drugs was evaluated in terms of body weight,syrup partiality and open field test.The changes of glutamic acid(GLU),gama-aminobutyric acid(GABA)serum hypothalamic-pituitaryadrenal(HPA)axis transmitters,IL-1 and other cytokines in the hippocampus and cortex of rats in each group were determined.The difference in chemical composition between Dingzhixiaowan and Kaixinwan pills was analyzed.Results Dingzhixiaowan significantly increased the body weight,glycemic preference and open field scores of CUMS rats,reduced GLU content in the hippocampus and cortex of rats,increased GABA content,reduced HPA axis transmitters,and regulated serum cytokine levels.Kaixinwan increased GABA content in the hippocampus and cortex of model rats,but reduced serum cytokine levels.Conclusion Dingzhixiaowan pills have obvious antidepressant effect,but Kaixinwan pills do not in behavioral experiments.The antidepressant effect of Dingzhixiaowan may be related to the regulation of central neuron amino acid secretion,reversal of the hyperactivity of HPA axis,and reduction of the immune regulation of IL-1 and other cytokines.The antidepressant effect of the prescription may be closely related to the content of main chemical components such as ginsenosides.

关 键 词：抑郁症 定志小丸 开心丸 慢性不可预知性温和应激抑郁模型 

分 类 号：R971[医药卫生—药品]