槟榔对小鼠的抗抑郁作用影响及机制研究  

Antidepressant effect of Areca catechu L.on mice and its mechanism

作　　者：裴海月 姜宁 王孟迪 王凤忠[1] 敖冬梅[3] 王琼 PEI Haiyue;JIANG Ning;WANG Mengdi;WANG Fengzhong;AO Dongmei;WANG Qiong(Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences,Beijing 100193,China;Sino-Portugal TCM International Cooperation Center,the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000;Beijing City College,Beijing 100094;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100193)

机构地区：[1]中国农业科学院农产品加工研究所,北京100193 [2]西南医科大学附属中医医院中葡中医药国际合作中心/中西医结合学院,四川泸州646000 [3]北京城市学院,北京100094 [4]中国医学科学院北京协和医学院药用植物研究所药理毒理研究中心,北京100193

出　　处：《中国比较医学杂志》2022年第1期24-32,共9页Chinese Journal of Comparative Medicine

基　　金：中国农业科学院农产品加工研究所创新工程院所重点任务(CAAS-ASTIP-2020-IFST);泸州市高端人才引进项目(刘新民团队);国家重点研发计划(2016YFE0131800)。

摘　　要：目的研究槟榔对小鼠抑郁样行为的影响及其作用机制。方法分别建立行为绝望模型和利血平拮抗模型,雄性ICR小鼠分为槟榔低、中、高剂量组(160、320、640 mg/kg)和阳性药组(氟西汀,20 mg/kg),连续灌胃给药14 d。采用行为学检测小鼠旷场实验(OFT)、悬尾实验(TST)及小鼠强迫游泳实验(FST)评价槟榔的抗抑郁活性;采用利血平拮抗实验评价槟榔的抗抑郁作用和槟榔对单胺能神经系统功能的影响以及其氧化应激水平的改变。采用本课题组建立的LC-MS/MS分析方法测定小鼠神经递质含量;通过超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量反映槟榔抗氧化应激水平。结果各组间体重均无显著性差异。旷场实验结果显示,槟榔对小鼠的自发活动情况无影响。槟榔中、高剂量组可显著降低悬尾不动时间(P<0.05,P<0.01),低、高剂量组可明显减少小鼠在强迫游泳实验中的不动时间(P<0.05)。在利血平拮抗实验中与模型组相比,槟榔低、高剂量组可拮抗利血平导致的小鼠体温降低(P<0.01),且3个剂量组均可显著拮抗利血平引起的小鼠眼睑下垂(P<0.05)。与利血平拮抗模型组相比,槟榔高剂量组小鼠脑组织中5-HT含量(P<0.01),槟榔低、高剂量组DA含量(P<0.05,P<0.01);槟榔低、中剂量组GABA水平(P<0.05)均有显著性升高;槟榔中、高剂量组5-HIAA水平均显著降低(P<0.01)。槟榔3个剂量组SOD和CAT活性均显著增强(P<0.01,P<0.01);槟榔中、高剂量组MDA含量显著下降(P<0.01)。结论槟榔在应激类绝望模型和利血平拮抗药物模型中均表现出较好的抗抑郁疗效且未影响运动活性及体重。其抗抑郁的作用机制可能与增强脑内单胺神经能系统水平及抗氧化应激水平相关。Objective To study the effect of Areca catechu L.on depression-like behavior in mice and its mechanism.Methods Behavioral despair and reserpine antagonism models were established.Male ICR mice were divided into Areca catechu L.low,medium and high dose groups(160,320 and 640 mg/kg)and a positive control group(fluoxetine,20 mg/kg).Administration was performed by continuous gavage for 14 days.The antidepressant activity of Areca catechu L.was evaluated by the behavioral test of open field test,tail suspension test and forced swimming test.The antidepressant effect of Areca catechu L.was also evaluated by the reserpine antagonism test to evaluate the effect of Areca catechu L.on monoaminergic nervous system functions and the change of oxidative stress level.The content of neurotransmitters in mice was determined by LC-MS/MS analysis.The anti-oxidative stress effect of Areca catechu L.was assessed by measuring superoxide dismutase(SOD),malondialdehyde(MDA)and catalase(CAT).Results There were no significant differences in body weight between the groups.The open field text showed that Areca catechu L.had no effect on the locomotor activity of mice.The medium and high dose groups of Areca catechu L.had significantly reduced time in the tail suspension test(P<0.05),and the low and high dose groups of Areca catechu L.had significantly reduced immobility time of mice in the forced swimming test(P<0.05).In the reserpine antagonism test,compared with the model group,the low and high dose groups of Areca catechu L.had antagonized eyelid ptosis induced by reserpine(P<0.05),and the three doses significantly antagonized the decrease of body temperature induced by reserpine(P<0.01).Compared with reserpine antagonism model group,the 5-HT content in the brain tissue of mice in the Areca catechu L.high dose group(P<0.01),DA content in Areca catechu L.low and high dose groups(P<0.01),and the GABA level in the Areca catechu L.low-and medium-dose groups(P<0.05)were significantly increased and the 5-HIAA level in Areca catechu L.medium a

关 键 词：槟榔 抑郁 利血平 悬尾 强迫游泳 神经递质 氧化应激 

分 类 号：R-33[医药卫生]