愤怒郁怒情绪反应及其诱发PMS病证结合猕猴模型的建立及评价
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摘要
目的:完成制备愤怒郁怒情绪反应及其诱发PMS肝气逆、肝气郁证猕猴模型的制备及评价,为探索愤怒郁怒致病机理提供适宜的载体平台;检测猕猴月经周期不同时期血清及中枢神经递质含量变化,初步揭示愤怒郁怒情绪诱发情志病证的发病机制;以中药经前平和经前舒颗粒对PMS模型猕猴进行干预,为阐明其作用机理提供有价值的线索。
方法:应用社会层级压力应激法(Social Subordination Stress)诱导猕猴出现情绪反应,然后依据《雌性实验猕猴情绪评价量表》(以下简称“量表”)评分配合实验猕猴面部表情计算机模式识别系统(以下简称“模式识别系统”)筛选出愤怒郁怒情绪反应猕猴模型,选取上述猕猴配合择时挤压造模使猕猴出现PMS肝气逆、肝气郁表现,随后采用量表评分和模式识别系统辅助判别其表情行为,最后应用中药经前平颗粒对PMS肝气逆证、经前舒颗粒对PMS肝气郁证进行干预。采集月经周期不同时期猕猴血清,分析血清和不同脑区NE、DA、5-HT和GABA(仅脑区)含量,结合量表评分结果,辅助模型评价,反证造模效果。
结果:愤怒、郁怒情绪反应猕猴愤怒因子积分均显著高于对照组(P<0.01),愤怒情绪组又显著高于郁怒情绪组(P<0.05),郁怒情绪反应猕猴抑郁因子积分显著高于对照组和愤怒情绪反应组(P<0.01),经前平和经前舒颗粒可显著降低PMS肝气逆、郁证猕猴愤怒、抑郁因子积分(P<0.05)。与对照组和情绪反应组相比,PMS肝气逆、郁证造模组血清单胺类神经递质含量显著升高(P<0.05, P<0.01),经前平和经前舒颗粒给药后均显著下降(P<0.05, P<0.01)。相较于对照组,PMS肝气逆证造模组垂体DA、下丘脑NE、DA,顶区皮质NE、DA、5-HT上升(P<0.05, P<0.01),垂体NE、GABA下降(P<0.05, P<0.01);PMS肝气郁证造模组垂体DA、GABA,下丘脑和顶区皮质NE、DA、5-HT,额区皮质GABA升高(P<0.05, P<0.01),垂体NE,GABA,垂体、下丘脑和顶区皮质GABA含量降低(P<0.05, P<0.01)。
结论:社会层级压力应激法造模能较好诱导出实验猕猴出现愤怒郁怒情绪,主观观测、量表评分及神经递质检测结果可作为评价实验猕猴愤怒郁怒情绪及病症表现的较好测量方法。愤怒郁怒情绪与血清单胺类神经递质变化有关,PMS肝气逆、郁证发病与血清及中枢单胺类神经递质和中枢GABA含量密切相关。经前平和经前舒颗粒调整血清及中枢神经递质紊乱可能是其分别用于治疗PMS肝气逆、郁证的重要作用机制。
Objective:To complete the establishment and evaluation of anger-out,anger-in emotion and induced PMS Liver-qi invasion,Liver-qi depression rhesus monkey models,and then provide an appropriate platform for studing pathogenic mechanism of anger-out and anger-in emotion; After detection of neurotransmitters in central and serum, pathogenesis of emotional syndromes induced by anger-out and anger-in emotion maybe initially revealed;In order to provide valuable clues for clarifying Jingqianping and Jingqianshu granule’actional mechanism,we intervened PMS model monkeys with these two drugs.
Methods: Experimental macaques were induced to show up emotional reaction with social level stress method,then anger-in,anger-out emotion macaques were screened by Emotional Evaluation Scale about Female Experiment Macaque scoring together with facial expression pattern recognition system,based on mentioned above experimental macaques were induced to show up PMS Liver-qi invasion and Liver-qi depression appearance combined with timing extrusion modeling,soon after their facial expression and behavior was secondary evaluated by scale scoring and pattern recognition, eventually Traditional Chinese Medicine Jingqianping and Jingqianshu Granule were respectively used to interfere.Serum of different periods were collected,then it was detected with different brain regions of norepinephrine,dopamine,5- hydroxytryptamine andγ- Aminobutyric Acid(only in brain regions) content,then the results combined with scale scoring were used to evaluate the models and to verify the effects of modeling.
Results: The angry factor scores of anger-in,anger-out rhesus monkeys were significantly higher than the control(P<0.01),anger-out group higer than anger-in group(P<0.05).The depression factor scores of anger-in rhesus monkeys were notably higer than the control and the anger-out(P<0.01), Jingqianping and Jingqianshu granule respectively lower the angry and depression factor scores of PMS Liver-qi invasion and Liver-qi depression rhesus monkeys(P<0.05).Contrary to the control and emotional reaction group,the monoamine neurotransmitters content of PMS liver-qi invasion and Liver-qi depression rhesus monkeys increased substantially(P<0.05, P<0.01),then decreased to a large extent administrated with Jingqianping and Jingqianshu granule(P<0.05, P<0.01).Compared with the control group, NE and DA content in hypothalamus,NE,DA and 5-HT content in parietal cortex of PMS Liver-qi invasion group was significantly higher(P<0.05, P<0.01),NE and GABA content in pituitary was lower(P<0.05, P<0.01); DA and GABA content in pituitary,NE,DA and 5-HT content in hypothalamus and parietal cortex,GABA content in frontal cortex increased significantly(P<0.05, P<0.01),GABA content in pituitary, hypothalamus and frontal cortex lowerd(P<0.05, P<0.01).
Conclusions:Rhesus monkeys could be induced to show anger-out and anger-in emotion with social level stress method, subjective observation, scale scoring and neurotransmitters detection could properly quantitate anger-out,anger-in emotion and symptoms of the disease.Anger-out and anger-in emotion had an relationship with the change of monoamine neurotransmitters content in serum , pathogenesis of PMS Liver-qi invasion and Liver-qi depression was closely related to monoamine neurotransmitters in serum and brain and GABA in brain.The regulation of neurotransmitters in serum and brain of Jingqianping and Jingqianshu Granule may be the mechanisms of treating PMS Liver-qi invasion and Liver-qi depression.
方法:应用社会层级压力应激法(Social Subordination Stress)诱导猕猴出现情绪反应,然后依据《雌性实验猕猴情绪评价量表》(以下简称“量表”)评分配合实验猕猴面部表情计算机模式识别系统(以下简称“模式识别系统”)筛选出愤怒郁怒情绪反应猕猴模型,选取上述猕猴配合择时挤压造模使猕猴出现PMS肝气逆、肝气郁表现,随后采用量表评分和模式识别系统辅助判别其表情行为,最后应用中药经前平颗粒对PMS肝气逆证、经前舒颗粒对PMS肝气郁证进行干预。采集月经周期不同时期猕猴血清,分析血清和不同脑区NE、DA、5-HT和GABA(仅脑区)含量,结合量表评分结果,辅助模型评价,反证造模效果。
结果:愤怒、郁怒情绪反应猕猴愤怒因子积分均显著高于对照组(P<0.01),愤怒情绪组又显著高于郁怒情绪组(P<0.05),郁怒情绪反应猕猴抑郁因子积分显著高于对照组和愤怒情绪反应组(P<0.01),经前平和经前舒颗粒可显著降低PMS肝气逆、郁证猕猴愤怒、抑郁因子积分(P<0.05)。与对照组和情绪反应组相比,PMS肝气逆、郁证造模组血清单胺类神经递质含量显著升高(P<0.05, P<0.01),经前平和经前舒颗粒给药后均显著下降(P<0.05, P<0.01)。相较于对照组,PMS肝气逆证造模组垂体DA、下丘脑NE、DA,顶区皮质NE、DA、5-HT上升(P<0.05, P<0.01),垂体NE、GABA下降(P<0.05, P<0.01);PMS肝气郁证造模组垂体DA、GABA,下丘脑和顶区皮质NE、DA、5-HT,额区皮质GABA升高(P<0.05, P<0.01),垂体NE,GABA,垂体、下丘脑和顶区皮质GABA含量降低(P<0.05, P<0.01)。
结论:社会层级压力应激法造模能较好诱导出实验猕猴出现愤怒郁怒情绪,主观观测、量表评分及神经递质检测结果可作为评价实验猕猴愤怒郁怒情绪及病症表现的较好测量方法。愤怒郁怒情绪与血清单胺类神经递质变化有关,PMS肝气逆、郁证发病与血清及中枢单胺类神经递质和中枢GABA含量密切相关。经前平和经前舒颗粒调整血清及中枢神经递质紊乱可能是其分别用于治疗PMS肝气逆、郁证的重要作用机制。
Objective:To complete the establishment and evaluation of anger-out,anger-in emotion and induced PMS Liver-qi invasion,Liver-qi depression rhesus monkey models,and then provide an appropriate platform for studing pathogenic mechanism of anger-out and anger-in emotion; After detection of neurotransmitters in central and serum, pathogenesis of emotional syndromes induced by anger-out and anger-in emotion maybe initially revealed;In order to provide valuable clues for clarifying Jingqianping and Jingqianshu granule’actional mechanism,we intervened PMS model monkeys with these two drugs.
Methods: Experimental macaques were induced to show up emotional reaction with social level stress method,then anger-in,anger-out emotion macaques were screened by Emotional Evaluation Scale about Female Experiment Macaque scoring together with facial expression pattern recognition system,based on mentioned above experimental macaques were induced to show up PMS Liver-qi invasion and Liver-qi depression appearance combined with timing extrusion modeling,soon after their facial expression and behavior was secondary evaluated by scale scoring and pattern recognition, eventually Traditional Chinese Medicine Jingqianping and Jingqianshu Granule were respectively used to interfere.Serum of different periods were collected,then it was detected with different brain regions of norepinephrine,dopamine,5- hydroxytryptamine andγ- Aminobutyric Acid(only in brain regions) content,then the results combined with scale scoring were used to evaluate the models and to verify the effects of modeling.
Results: The angry factor scores of anger-in,anger-out rhesus monkeys were significantly higher than the control(P<0.01),anger-out group higer than anger-in group(P<0.05).The depression factor scores of anger-in rhesus monkeys were notably higer than the control and the anger-out(P<0.01), Jingqianping and Jingqianshu granule respectively lower the angry and depression factor scores of PMS Liver-qi invasion and Liver-qi depression rhesus monkeys(P<0.05).Contrary to the control and emotional reaction group,the monoamine neurotransmitters content of PMS liver-qi invasion and Liver-qi depression rhesus monkeys increased substantially(P<0.05, P<0.01),then decreased to a large extent administrated with Jingqianping and Jingqianshu granule(P<0.05, P<0.01).Compared with the control group, NE and DA content in hypothalamus,NE,DA and 5-HT content in parietal cortex of PMS Liver-qi invasion group was significantly higher(P<0.05, P<0.01),NE and GABA content in pituitary was lower(P<0.05, P<0.01); DA and GABA content in pituitary,NE,DA and 5-HT content in hypothalamus and parietal cortex,GABA content in frontal cortex increased significantly(P<0.05, P<0.01),GABA content in pituitary, hypothalamus and frontal cortex lowerd(P<0.05, P<0.01).
Conclusions:Rhesus monkeys could be induced to show anger-out and anger-in emotion with social level stress method, subjective observation, scale scoring and neurotransmitters detection could properly quantitate anger-out,anger-in emotion and symptoms of the disease.Anger-out and anger-in emotion had an relationship with the change of monoamine neurotransmitters content in serum , pathogenesis of PMS Liver-qi invasion and Liver-qi depression was closely related to monoamine neurotransmitters in serum and brain and GABA in brain.The regulation of neurotransmitters in serum and brain of Jingqianping and Jingqianshu Granule may be the mechanisms of treating PMS Liver-qi invasion and Liver-qi depression.
引文
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