栀子提取物GJ-4对利血平致抑郁症小鼠的作用及机制研究  

Pharmacodynamics and Mechanistic Study of Gardeniae Fructus Extract GJ-4 on Depressed Mice Induced by Reserpine

作　　者：李方园 盛婵娟 袁方玉 鞠程 尚俊美 鲍秀琦 张丹 LI Fangyuan;SHENG Chanjuan;YUAN Fangyu;JU Cheng;SHANG Junmei;BAO Xiuqi;ZHANG Dan(State Key Laboratory of Natural Products and Functions,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院,北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《中药新药与临床药理》2021年第6期751-757,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：医科院创新工程重大协同创新项目(500104122);国家自然科学基金资助项目(81630097,81773718);中国医学科学院医学与健康科技创新工程资助项目(2016-I2M-3-011);中国医学科学院中央高校基本科研业务费项目(2018RC35002);重大新药创制科技重大专项“十三五”计划项目(2018ZX09711001-003-020,2018ZX09711001-003-005,2018ZX09711001-008-005)。

摘　　要：目的探讨栀子提取物GJ-4对利血平致抑郁症小鼠的作用及机制。方法将ICR小鼠随机分为正常对照组、模型组(利血平组)、氟西汀组(阳性药组,20 mg·kg^(-1))及GJ-4低、中、高剂量组(25、50、100 mg·kg^(-1)),每组17只;灌胃给药,每日1次,连续14 d。灌胃给药30 min后,采用腹腔注射利血平(0.2 mg·kg^(-1))复制抑郁症小鼠模型。采用观察眼睑下垂程度、旷场实验、悬尾实验、糖水偏好实验等行为学方法评价小鼠的抑郁状态;采用荧光法测定小鼠脑皮层单胺氧化酶A(MAO-A)的含量;高效液相色谱-电化学检测法测定小鼠脑皮层内单胺类神经递质[多巴胺(DA)、去甲肾上腺素(NE)、高香草酸(HAV)、二羟基苯乙酸(DOPAC)、5-羟色胺(5-HT)]的含量。结果与正常对照组比较,模型组小鼠的眼睑下垂程度评分明显提高(P<0.001);运动功能明显受到抑制,走出格子的潜伏期明显延长(P<0.001),通过格子数明显减少(P<0.001);悬尾6 min内的不动时间显著增加(P<0.001);糖水偏好系数明显降低,糖水的消耗量明显下降(P<0.001);小鼠脑皮层内MAO-A的含量明显上升(P<0.001),DA、DOPAC、5-HT、HAV含量均明显下降(P<0.01,P<0.001)。与模型组比较,各给药组小鼠眼睑下垂程度评分明显降低(P<0.001);GJ-4中、高剂量组小鼠走出格子的潜伏期明显缩短(P<0.001),GJ-4高剂量组小鼠通过的格子数明显增加(P<0.05);各给药组小鼠的悬尾不动时间明显缩短(P<0.001);GJ-4低、中、高剂量组小鼠的糖水偏好系数明显升高,糖水消耗量明显增加(P<0.05,P<0.01,P<0.001);GJ-4高剂量组小鼠脑皮层内MAO-A的含量明显降低(P<0.001),DOPAC、5-HT含量明显升高(P<0.01,P<0.001)。结论GJ-4对利血平致抑郁症模型小鼠具有明显的抗抑郁活性,其机制可能与抑制脑内MAO-A的活性,增加脑内5-HT和DOPAC的含量有关。Objective To investigate the effect and mechanism of Gardeniae fructus extract GJ-4 on reserpine induced depression mice.Methods ICR mice were randomly divided into control group,model group(reserpine group),fluoxetine group(positive group,20 mg·kg^(-1)),GJ-4 low-dose,medium-dose and high-dose groups(25,50,100 mg·kg^(-1)),with 17 mice in each group.The drugs were given by gavage once a day for consecutive 14 days.30 min after intragastric administration,reserpine(0.2 mg·kg^(-1))was injected intraperitoneally to establish depressed mice model.The depression status of mice was evaluated by observing the blepharoptosis,open field test,tail suspension test,sugar water preference test and other behavioral methods.The content of monoamine oxidase A(MAO-A)in the cerebral cortex of mice was determined by fluorescence method.The contents of monoamine neurotransmitters dopamine(DA),norepinephrine(NE),vanillic acid(HAV),dihydroxy phenylacetic acid(DOPAC),5-hydroxytryptamine(5-HT)in the cerebral cortex of mice were determined by high performance liquid chromatography combined with electrochemical method.Results Compared with control group,the score of blepharoptosis in model group was significantly increased(P<0.001).The motor function was significantly injured,the latency of getting out of the cell was significantly prolonged(P<0.001),and the number of cells passed was significantly decreased(P<0.001).The immobility time within 6 min of tail suspension was significantly increased(P<0.001).The sugar water preference coefficient was significantly decreased,and the consumption of sugar water was significantly decreased(P<0.001).The content of MAO-A in cerebral cortex of mice was significantly increased(P<0.001),while the contents of DA,DOPAC,5-HT and HAV were significantly decreased(P<0.01,P<0.001).Compared with model group,blepharoptosis scores of the mice in each dose group of GJ-4 was significantly decreased(P<0.001).The latency of getting out of the cell in GJ-4 high and medium dose groups was significantly shortened(P<

关 键 词：栀子提取物GJ-4 利血平 抑郁症 小鼠 单胺氧化酶A 单胺类递质 5-羟色胺 二羟基苯乙酸 

分 类 号：R285.5[医药卫生—中药学]