DL-3-正丁基邻苯二甲酸对慢性酒精中毒小鼠情绪记忆的影响及其机制

中华行为医学与脑科学杂志 Pub Date : 2020-01-20 DOI:10.3760/CMA.J.CN371469-20190624-00401

Ting-Mei Wang, Bo Xiang, Guohua Wang, X. Liang, Kezhi Liu

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Ang the mice in AT group and CON group was given the same dose of corn oil by gavage.Open field test was used to evaluate anxiety-like behavior, tail suspension test to evaluate depression-like behavior, Morris water maze and new object recognition to evaluate memory ability, and TUNEL staining to evaluate the number of neuron apoptosis. The primary cultured neurons were interfered by alcohol and NBP at the cell level, and the calcium concentration in the neurons was detected by fluorescence calcium imaging. Descriptive analysis, t-test and one-way ANOVA were processed by SPSS 17.0. \n \n \nResults \nThe results of open field test showed that the exploration time of AT+ NBP group was longer than that of AT group ((50.68±7.82)s, (38.50±13.93)s; t=-2.16, P<0.05)). In the spatial memory test, the target quadrant exploration time of AT+ NBP group was longer than that of AT group ((28.02±7.13)s, (20.98±5.58)s; t=-2.20, P<0.05). In short memory test, the cognitive coefficient RI (0.83±0.08) of AT+ NBP group was higher than that of AT group (0.68±0.10) (t=-3.13, P<0.05). Compared with CON group, the number of neuron apoptosis in prefrontal cortex in AT group increased ((17.33±2.51), (115.67±6.50); t=-24.41, P<0.001), and that in AT+ NBP group decreased compared with AT group((45.00±5.57)) (t=14.29, P<0.001). The number of apoptosis neurons in the dentate gyrus of the hippocampus in AT group (13.75±4.79) was also less than that in the AT+ NBP group (5.75±3.30) (t=2.75, P<0.05). Calcium concentration in nerve cells was detected that the three concentrations of alcohol (100 mmol/L, 200 mmol/L and 300 mmol/L) led to a significant increase in the RFU within the nerve cells (△F/F) ((1.43±0.32), (2.31±1.39), (1.21±0.73); t=-7.67, -2.85, -2.86, all P<0.05). 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引用次数: 0

摘要

目的探讨dl-3-正丁基邻苯二甲酸（NBP）对慢性酒精中毒模型小鼠情绪记忆的改善作用及其可能机制。方法24只成年雄性C57/BL6小鼠随机分为对照组（CON，n=8）、模型组（AT，n=8。AT组和AT+NBP组小鼠灌胃灌胃，建立慢性酒精中毒模型。在AT+NBP组中，在酒精建模期间，小鼠每天灌胃一次NBP（40mg/kg），持续14天。Ang AT组和CON组小鼠灌胃给予相同剂量的玉米油。开放场试验用于评估焦虑样行为，尾悬试验用于评估抑郁样行为，Morris水迷宫和新物体识别用于评估记忆能力，TUNEL染色用于评估神经元凋亡数量。原代培养的神经元在细胞水平上受到酒精和NBP的干扰，并通过荧光钙成像检测神经元中的钙浓度。采用SPSS 17.0进行描述性分析、t检验和单因素方差分析。结果野外试验结果表明，AT+NBP组探查时间比AT组长（（50.68±7.82）s，（38.50±13.93）s；在空间记忆测试中，AT+NBP组的目标象限探索时间比AT组长（（28.02±7.13）s，（20.98±5.58）s；在短记忆测试中，AT+NBP组的认知系数RI（0.83±0.08）高于AT组（0.68±0.10）（t=-3.13，P<0.05）。与CON组相比，AT组前额叶皮层神经元凋亡数量增加（（17.33±2.51），（115.67±6.50）；t=-24.41，P＜0.001），AT+NBP组海马齿状回凋亡神经元数（13.75±4.79）明显少于AT+NBP组（5.75±3.30）（t=2.75，P<0.05）导致神经细胞内RFU显著增加(△F/F）（（1.43±0.32），（2.31±1.39），（1.21±0.73）；t=-7.67，-2.85，-2.86，均P<0.05）。NBP治疗三组RFU变化相对稳定（（0.04±0.01），（-0.03±0.01）和（-0.04±0.02）；t=7.96,2.96,2.92，均P<0.05）。结论3-丁基邻苯二甲酸酯能改善慢性酒精中毒模型小鼠的学习记忆能力，这可能与抑制神经元凋亡和影响细胞内钙稳态有关。关键词：DL-3-正丁基邻苯二甲酸酯；酗酒；焦虑；记忆；神经元凋亡；钙稳态

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Effect and mechanism of DL-3-n-butylphthalide on emotional memory in mice with chronic alcoholism

Objective To investigate the improvement and possible mechanism of dl-3-n-butylphthalide (NBP) on the emotional memory of chronic alcoholism model mice. Methods Twenty-four adult male C57/BL6 mice were randomly divided into control group (CON, n=8), model group (AT, n=8), treatment group (AT+ NBP, n=8). Mice in AT group and AT+ NBP group were administrated with alcohol to establish chronic alcoholism model. In the AT+ NBP group, the mice was administrated with NBP (40 mg/kg) by gavage once a day for 14 days during the alcohol modeling period. Ang the mice in AT group and CON group was given the same dose of corn oil by gavage.Open field test was used to evaluate anxiety-like behavior, tail suspension test to evaluate depression-like behavior, Morris water maze and new object recognition to evaluate memory ability, and TUNEL staining to evaluate the number of neuron apoptosis. The primary cultured neurons were interfered by alcohol and NBP at the cell level, and the calcium concentration in the neurons was detected by fluorescence calcium imaging. Descriptive analysis, t-test and one-way ANOVA were processed by SPSS 17.0. Results The results of open field test showed that the exploration time of AT+ NBP group was longer than that of AT group ((50.68±7.82)s, (38.50±13.93)s; t=-2.16, P<0.05)). In the spatial memory test, the target quadrant exploration time of AT+ NBP group was longer than that of AT group ((28.02±7.13)s, (20.98±5.58)s; t=-2.20, P<0.05). In short memory test, the cognitive coefficient RI (0.83±0.08) of AT+ NBP group was higher than that of AT group (0.68±0.10) (t=-3.13, P<0.05). Compared with CON group, the number of neuron apoptosis in prefrontal cortex in AT group increased ((17.33±2.51), (115.67±6.50); t=-24.41, P<0.001), and that in AT+ NBP group decreased compared with AT group((45.00±5.57)) (t=14.29, P<0.001). The number of apoptosis neurons in the dentate gyrus of the hippocampus in AT group (13.75±4.79) was also less than that in the AT+ NBP group (5.75±3.30) (t=2.75, P<0.05). Calcium concentration in nerve cells was detected that the three concentrations of alcohol (100 mmol/L, 200 mmol/L and 300 mmol/L) led to a significant increase in the RFU within the nerve cells (△F/F) ((1.43±0.32), (2.31±1.39), (1.21±0.73); t=-7.67, -2.85, -2.86, all P<0.05). In comparison, the changes of RFU in the three groups treated with NBP treatment were relatively stable ((0.04±0.01), (-0.03±0.01), (-0.04±0.02); t=7.96, 2.96, 2.92, all P< 0.05). Conclusion The 3-n-Butylphthalide can improve the learning and memory ability of chronic alcoholism model mice, which may be related with the inhibition of neuron apoptosis and the influence of intracellular calcium homeostasis. Key words: DL-3-n-Butylphthalide; Alcoholism; Anxiety; Memory; Neuronal apoptosis; Calcium homeostasis

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来源期刊

中华行为医学与脑科学杂志

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期刊介绍： "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.