心身疾病刚柔辨证的脑电图及脑内神经递质活性的超慢涨落图分析
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摘要
研究目的
从大脑皮层功能改变和脑内神经递质活性方面揭示中医心身医学“刚柔辨证”理论的物质基础和证候实质,为“刚柔辨证”证病结合起到示范研究作用。
研究方法
本研究以“证病结合”、“以方测证”、“一病一结”为研究方法,以脑电信号为切入点,采用脑电信号线性分析法(脑电图频域分析法)和非线性分析法(脑电超慢涨落分析法)为技术手段,把经显效方剂对应治疗2-8周后疗效为显效和临床痊愈的“刚柔辨证”主证为心肝火旺、心肝阴虚、肝郁气滞、肝郁脾虚证的患者治疗前脑电图及脑电超慢涨落图加以分析。其中,心肝火旺证为“刚证实证”代表,心肝阴虚证为“刚证虚证”代表,肝郁气滞证为“柔证实证”代表,肝郁脾虚证为“柔证虚证”代表。比较“刚柔”具有代表性的四种证候在脑电图上脑区、节律、功率值的变化及在超慢涨落图上脑内神经递质激活情况的变化。共入组病例100例,其中心肝火旺证20例、心肝阴虚证32例、肝郁气滞证27例和肝郁脾虚证21例。健康人对照组23例。脑电图及脑电超慢涨落图由北京太阳电子科技公司生产的SOLAR1848系列定量数字脑电图仪测量。将所有数据整理后输入数据库,用SPSS18.0统计软件进行统计分析,采用一般描述性分析,独立样本或配对样本的t检验,多个样本的单因素方差分析(One-way ANOVA),多个样本的非参数检验Kruskal-Wallis H方法和卡方检验等方法。双侧检验,取a=0.05,取P<0.05或P<0.01为差异有统计学意义。
研究结果
(1)四个证型与对照组比较在脑电地形图上的规律性及特异性改变：
①心肝火旺证、肝郁气滞证、肝郁脾虚证三证型在脑电地形图上有脑区、节律、功率值的大致相同的表现趋势：慢波功率值均增高,以前头部为主(P<0.05)；顶枕区α功率值减低(P<0.01)；额极区、额区(P<0.01)及枕区(P<0.05)β功率值减低。三证型的不同点是肝郁脾虚证的慢波节律出现范围较其他两证型除额极区外增加了额区及中央区(P<0.05),慢波出现的范围更广些。心肝火旺证的慢波节律除了0活动增多外,较其他二个证型增加了δ波活动(P<0.05),慢波节律更慢。
②心肝阴虚证较其他三个证型在脑电地形图上有特异性表现：在除了双颞区之外所有12个脑区慢波功率值均见增高趋势,慢波增多范围更为广泛,且包括慢波θ波(P<0.05)和6波(P<0.01),慢波节律有更慢趋势。a节律有前移和泛化趋势(P<0.01),且顶枕区的α波优势部分抑制或抑制程度较轻；额极区、额区可见p功率值减低(P<0.05)。
(2)四个证型与对照组比较在脑电超慢涨落图上的脑内神经递质活性的规律性及特异性改变：
①右额叶联合区的多巴胺(DA)能活动的减低可能是“刚柔辨证”理论大脑功能改变的共同的物质基础之一(P<0.05)。
②左中颞区(T3区)可能是“刚柔辨证”理论脑功能改变的主要脑区之一(P<0.05)。
③左中颞区(T3区)的兴奋性介质(EXC)激活水平减低、抑制性介质(INH)激活水平增高的两者协同作用,可能是“刚柔辨证”之“刚证”的脑功能改变的物质基础之一(P<0.05)。
④全脑EXC激活水平减低可能是“刚柔辨证”心肝火旺证、心肝阴虚证、肝郁气滞证三个证型的脑功能改变的物质基础之一(P<0.05)。
⑤左中颞区(T3区)的乙酰胆碱(ACh)与去甲肾上腺素(NE)激活水平异常的协同关系及5-羟色胺(5-HT)与DA激活水平异常的协同关系可能为心肝阴虚证脑功能改变的物质基础之一(P<0.05)。
⑥左额叶联合区的NE激活水平异常可能是肝郁气滞证脑功能改变的物质基础之一(P<0.05)。
⑦左中颞区(T3区)INH激活水平升高可能为肝郁脾虚证脑功能改变的物质基础之一(P<0.05)。
结论
(1)本研究所得结论已经部分揭示出心身疾病“刚柔辨证”的“刚柔”不同证候在脑电图上有脑区、频段、功率值的规律性和特异性表现,在脑电超慢涨落图上有脑内神经递质活性的规律性和特异性表现。初步从脑电生理学角度、大脑皮层功能改变方面和脑内神经递质活性改变方面,揭示出“刚柔辨证”理论的物质基础和证候实质。
(2)确立了中医心身疾病证候的研究模式,为“刚柔辨证”的“证病结合”研究模式起到示范作用。
(3)从脑电生理学角度、脑内神经递质活性角度可以制定出符合心身疾病“刚柔辨证”特点的诊断、疗效评价、筛选有效治疗药物及作用机制的靶指标。
(4)提示心身疾病患者心理社会负性刺激对大脑功能的影响,以致躯体可产生器质性改变或病理生理过程。为中医心身疾病(情志致病)理论“主明则下安,以此养生则寿”、“主不明则十二官危,使道闭塞不通,形乃大伤”提供了现代医学脑电生理学证据。
(5)在脑电生理这一层面为证候的物质基础研究提供现代科学证据。
Objective:To explore the material bases and the nature of'Rigid-Gentle Syndrome Differentiation' of psychosomatic medicine from the aspects of cerebral cortex functions and brain neurotransmitters levels by the methods of electroencephalogram (EEG) and super encephalofluctuograph technology(SET).
Methods:Syndromes are the core while diseases are the complement. The accuracy of Syndrome Differentiation has been verifying by the curative effects of fixed traditional Chinese medicine (TCM) prescription. Each case was summarized by curative effects according to efficacy standards of different diseases. Brain electrical activity mapping (BEAM)(linear analysis method of EEG) and SET (nonlinear analysis of EEG) were used as technical means to measure the cerebral cortex functions and brain neurotransmitters levels. Each case has been measured by BEAM and SET before treatment.100cases of the four syndromes of'Hyperactivity of heart-fire and liver-fire','Heart and liver yin deficiency','Stagnation of QI due to depression of the liver'and'Stagnation of liver-QI with deficiency of the spleen' which belong to the system of'Rigid-Gentle Syndrome Differentiation' were enrolled in this study, and in order the number of cases are20,32,27and21. In addition, the control group is of23healthy volunteers. The differences of cortical areas, brain wave rhythms and power values in BEAM and neurotransmitters levels in SET have been compared among the four syndromes groups and the control group. The data was analyzed by SPSS18.0and the statistical methods are descriptive analysis, One-way ANOVA, Independent-samples T-test, Paired-samples T-test, and Kruskal-Wallis H test, Chi-square test and so on. All statistical tests were two-sided (a=0.05).There is a significant difference if p valve is less than0.05or0.01.
Results:
(1) The regularities and specificities of four syndromes compared with control group in BEAM:
①The three syndromes of'Hyperactivity of heart-fire and liver-fire','Stagnation of QI due to depression of the liver'and'Stagnation of liver-QI with deficiency of the spleen' have roughly the same expressions in BEAM:the rising trend of slow wave power in the forebrain(P<0.05); the decreasing trend of α wave power in parietal-occipital region(P<0.01); the decreasing trend of β wave power in frontal pole(P<0.01), frontaland parietal-occipital region(P<0.05). The different expressions in BEAM of these three syndromes were that a wider range of slow wave rhythm of'Stagnation of liver-QI with deficiency of the spleen' syndrome expanding to frontal and central region (P<0.05)beside frontal pole; a slower wave rhythm of 'Hyperactivity of heart-fire and liver-fire'syndrome including δ activity(P<0.05) besides0wave.
②The specificity of the syndrome of'Heart and liver yin deficiency'in BEAM:the rising trend of slow wave power including0wave(P<0.05) and8wave(P<0.01) in twelve cortical areas except double temporal region which is much wider than other three syndromes; forward and generalized trend of a wave rhythm (P<0.01)and no suppression of the ascendancy of a wave rhythm in parietal-occipital region; the decreasing trend of β wave power in frontal pole and frontal region(P<0.05).
(2)The regularities and specificities of four syndromes compared with control group in SET:
①The reduced activity of Dopamine(DA) in right Prefrontal Cortex maybe the one of common material bases of'Rigid-Gentle Syndrome Differentiation' theory in cerebral function changes(P<0.05).
②Left Mid-temporal3region(T3) maybe the main cerebral region of'Rigid-Gentle Syndrome Differentiation'theory in cerebral function changes(P<0.05).
③The co-operation of reduced activity of Excitatory Neurotransmitter (EXC) and increased activity of Inhibitory Neurotransmitter (INH) in T3maybe the one of material bases of'Rigid syndrome'in'Rigid-Gentle Syndrome Differentiation' theory(P<0.05).
④The reduced activity of EXC in brain maybe the one of common material bases of the three syndromes of'Hyperactivity of heart-fire and liver-fire','Heart and liver yin deficiency'and'Stagnation of QI due to depression of the liver'in cerebral function changes(P<0.05).
⑤The co-operation of Acetylcholine (ACh) and Norepinephrine(NE), and5-Hydroxytryptamine(5-HT) and DA in T3maybe the one of material bases of'Heart and liver yin deficiency' syndrome in cerebral function changes(P<0.05).
⑥The abnormal activity of NE in left Prefrontal Cortex maybe the one of material bases of'Stagnation of QI due to depression of the liver' syndrome in cerebral function changes.(P<0.05)
⑦The increased activity of INH in T3maybe the one of material bases of'Stagnation of liver-QI with deficiency of the spleen' syndrome in cerebral function changes(P<0.05).
Conclusions:
①The results of this study have partly revealed the regularities and specificities of four syndromes of'Rigid-Gentle Syndrome Differentiation' theory in BEAM and SET. This study has preliminarily provided the evidences of the material bases and the nature of'Rigid-Gentle Syndrome Differentiation' of psychosomatic medicine from the aspects of cerebral cortex functions and brain neurotransmitters levels.
②At same time, the research mode of'Syndromes are the core while diseases are the complement' has been established which will play a role of demonstration effect in the future study of'Rigid-Gentle Syndrome Differentiation'.
③This study also could set up target indexes for diagnosis, effectiveness evaluation, screening effective drugs and their mechanisms of psychosomatic diseases from the aspects of cerebral cortex functions and brain neurotransmitters levels.
④This study indicates that negative stimuli of psycho-social factors can affect cerebral function, which causes organic disorders or process of pathologic physiology. This study provides the brain electrophysiological evidence for the TCM psychosomatic medicine theory "If the mentality is normal, the organs will function normally. This is the fundamental principle to keep good health and a long life" and "If the mentality is abnormal, it is very dangerous to the twelve organs including itself."
⑤This study also provides modern scientific data for basic researches of TCM syndrome from the EEG signals.
从大脑皮层功能改变和脑内神经递质活性方面揭示中医心身医学“刚柔辨证”理论的物质基础和证候实质,为“刚柔辨证”证病结合起到示范研究作用。
研究方法
本研究以“证病结合”、“以方测证”、“一病一结”为研究方法,以脑电信号为切入点,采用脑电信号线性分析法(脑电图频域分析法)和非线性分析法(脑电超慢涨落分析法)为技术手段,把经显效方剂对应治疗2-8周后疗效为显效和临床痊愈的“刚柔辨证”主证为心肝火旺、心肝阴虚、肝郁气滞、肝郁脾虚证的患者治疗前脑电图及脑电超慢涨落图加以分析。其中,心肝火旺证为“刚证实证”代表,心肝阴虚证为“刚证虚证”代表,肝郁气滞证为“柔证实证”代表,肝郁脾虚证为“柔证虚证”代表。比较“刚柔”具有代表性的四种证候在脑电图上脑区、节律、功率值的变化及在超慢涨落图上脑内神经递质激活情况的变化。共入组病例100例,其中心肝火旺证20例、心肝阴虚证32例、肝郁气滞证27例和肝郁脾虚证21例。健康人对照组23例。脑电图及脑电超慢涨落图由北京太阳电子科技公司生产的SOLAR1848系列定量数字脑电图仪测量。将所有数据整理后输入数据库,用SPSS18.0统计软件进行统计分析,采用一般描述性分析,独立样本或配对样本的t检验,多个样本的单因素方差分析(One-way ANOVA),多个样本的非参数检验Kruskal-Wallis H方法和卡方检验等方法。双侧检验,取a=0.05,取P<0.05或P<0.01为差异有统计学意义。
研究结果
(1)四个证型与对照组比较在脑电地形图上的规律性及特异性改变：
①心肝火旺证、肝郁气滞证、肝郁脾虚证三证型在脑电地形图上有脑区、节律、功率值的大致相同的表现趋势：慢波功率值均增高,以前头部为主(P<0.05)；顶枕区α功率值减低(P<0.01)；额极区、额区(P<0.01)及枕区(P<0.05)β功率值减低。三证型的不同点是肝郁脾虚证的慢波节律出现范围较其他两证型除额极区外增加了额区及中央区(P<0.05),慢波出现的范围更广些。心肝火旺证的慢波节律除了0活动增多外,较其他二个证型增加了δ波活动(P<0.05),慢波节律更慢。
②心肝阴虚证较其他三个证型在脑电地形图上有特异性表现：在除了双颞区之外所有12个脑区慢波功率值均见增高趋势,慢波增多范围更为广泛,且包括慢波θ波(P<0.05)和6波(P<0.01),慢波节律有更慢趋势。a节律有前移和泛化趋势(P<0.01),且顶枕区的α波优势部分抑制或抑制程度较轻；额极区、额区可见p功率值减低(P<0.05)。
(2)四个证型与对照组比较在脑电超慢涨落图上的脑内神经递质活性的规律性及特异性改变：
①右额叶联合区的多巴胺(DA)能活动的减低可能是“刚柔辨证”理论大脑功能改变的共同的物质基础之一(P<0.05)。
②左中颞区(T3区)可能是“刚柔辨证”理论脑功能改变的主要脑区之一(P<0.05)。
③左中颞区(T3区)的兴奋性介质(EXC)激活水平减低、抑制性介质(INH)激活水平增高的两者协同作用,可能是“刚柔辨证”之“刚证”的脑功能改变的物质基础之一(P<0.05)。
④全脑EXC激活水平减低可能是“刚柔辨证”心肝火旺证、心肝阴虚证、肝郁气滞证三个证型的脑功能改变的物质基础之一(P<0.05)。
⑤左中颞区(T3区)的乙酰胆碱(ACh)与去甲肾上腺素(NE)激活水平异常的协同关系及5-羟色胺(5-HT)与DA激活水平异常的协同关系可能为心肝阴虚证脑功能改变的物质基础之一(P<0.05)。
⑥左额叶联合区的NE激活水平异常可能是肝郁气滞证脑功能改变的物质基础之一(P<0.05)。
⑦左中颞区(T3区)INH激活水平升高可能为肝郁脾虚证脑功能改变的物质基础之一(P<0.05)。
结论
(1)本研究所得结论已经部分揭示出心身疾病“刚柔辨证”的“刚柔”不同证候在脑电图上有脑区、频段、功率值的规律性和特异性表现,在脑电超慢涨落图上有脑内神经递质活性的规律性和特异性表现。初步从脑电生理学角度、大脑皮层功能改变方面和脑内神经递质活性改变方面,揭示出“刚柔辨证”理论的物质基础和证候实质。
(2)确立了中医心身疾病证候的研究模式,为“刚柔辨证”的“证病结合”研究模式起到示范作用。
(3)从脑电生理学角度、脑内神经递质活性角度可以制定出符合心身疾病“刚柔辨证”特点的诊断、疗效评价、筛选有效治疗药物及作用机制的靶指标。
(4)提示心身疾病患者心理社会负性刺激对大脑功能的影响,以致躯体可产生器质性改变或病理生理过程。为中医心身疾病(情志致病)理论“主明则下安,以此养生则寿”、“主不明则十二官危,使道闭塞不通,形乃大伤”提供了现代医学脑电生理学证据。
(5)在脑电生理这一层面为证候的物质基础研究提供现代科学证据。
Objective:To explore the material bases and the nature of'Rigid-Gentle Syndrome Differentiation' of psychosomatic medicine from the aspects of cerebral cortex functions and brain neurotransmitters levels by the methods of electroencephalogram (EEG) and super encephalofluctuograph technology(SET).
Methods:Syndromes are the core while diseases are the complement. The accuracy of Syndrome Differentiation has been verifying by the curative effects of fixed traditional Chinese medicine (TCM) prescription. Each case was summarized by curative effects according to efficacy standards of different diseases. Brain electrical activity mapping (BEAM)(linear analysis method of EEG) and SET (nonlinear analysis of EEG) were used as technical means to measure the cerebral cortex functions and brain neurotransmitters levels. Each case has been measured by BEAM and SET before treatment.100cases of the four syndromes of'Hyperactivity of heart-fire and liver-fire','Heart and liver yin deficiency','Stagnation of QI due to depression of the liver'and'Stagnation of liver-QI with deficiency of the spleen' which belong to the system of'Rigid-Gentle Syndrome Differentiation' were enrolled in this study, and in order the number of cases are20,32,27and21. In addition, the control group is of23healthy volunteers. The differences of cortical areas, brain wave rhythms and power values in BEAM and neurotransmitters levels in SET have been compared among the four syndromes groups and the control group. The data was analyzed by SPSS18.0and the statistical methods are descriptive analysis, One-way ANOVA, Independent-samples T-test, Paired-samples T-test, and Kruskal-Wallis H test, Chi-square test and so on. All statistical tests were two-sided (a=0.05).There is a significant difference if p valve is less than0.05or0.01.
Results:
(1) The regularities and specificities of four syndromes compared with control group in BEAM:
①The three syndromes of'Hyperactivity of heart-fire and liver-fire','Stagnation of QI due to depression of the liver'and'Stagnation of liver-QI with deficiency of the spleen' have roughly the same expressions in BEAM:the rising trend of slow wave power in the forebrain(P<0.05); the decreasing trend of α wave power in parietal-occipital region(P<0.01); the decreasing trend of β wave power in frontal pole(P<0.01), frontaland parietal-occipital region(P<0.05). The different expressions in BEAM of these three syndromes were that a wider range of slow wave rhythm of'Stagnation of liver-QI with deficiency of the spleen' syndrome expanding to frontal and central region (P<0.05)beside frontal pole; a slower wave rhythm of 'Hyperactivity of heart-fire and liver-fire'syndrome including δ activity(P<0.05) besides0wave.
②The specificity of the syndrome of'Heart and liver yin deficiency'in BEAM:the rising trend of slow wave power including0wave(P<0.05) and8wave(P<0.01) in twelve cortical areas except double temporal region which is much wider than other three syndromes; forward and generalized trend of a wave rhythm (P<0.01)and no suppression of the ascendancy of a wave rhythm in parietal-occipital region; the decreasing trend of β wave power in frontal pole and frontal region(P<0.05).
(2)The regularities and specificities of four syndromes compared with control group in SET:
①The reduced activity of Dopamine(DA) in right Prefrontal Cortex maybe the one of common material bases of'Rigid-Gentle Syndrome Differentiation' theory in cerebral function changes(P<0.05).
②Left Mid-temporal3region(T3) maybe the main cerebral region of'Rigid-Gentle Syndrome Differentiation'theory in cerebral function changes(P<0.05).
③The co-operation of reduced activity of Excitatory Neurotransmitter (EXC) and increased activity of Inhibitory Neurotransmitter (INH) in T3maybe the one of material bases of'Rigid syndrome'in'Rigid-Gentle Syndrome Differentiation' theory(P<0.05).
④The reduced activity of EXC in brain maybe the one of common material bases of the three syndromes of'Hyperactivity of heart-fire and liver-fire','Heart and liver yin deficiency'and'Stagnation of QI due to depression of the liver'in cerebral function changes(P<0.05).
⑤The co-operation of Acetylcholine (ACh) and Norepinephrine(NE), and5-Hydroxytryptamine(5-HT) and DA in T3maybe the one of material bases of'Heart and liver yin deficiency' syndrome in cerebral function changes(P<0.05).
⑥The abnormal activity of NE in left Prefrontal Cortex maybe the one of material bases of'Stagnation of QI due to depression of the liver' syndrome in cerebral function changes.(P<0.05)
⑦The increased activity of INH in T3maybe the one of material bases of'Stagnation of liver-QI with deficiency of the spleen' syndrome in cerebral function changes(P<0.05).
Conclusions:
①The results of this study have partly revealed the regularities and specificities of four syndromes of'Rigid-Gentle Syndrome Differentiation' theory in BEAM and SET. This study has preliminarily provided the evidences of the material bases and the nature of'Rigid-Gentle Syndrome Differentiation' of psychosomatic medicine from the aspects of cerebral cortex functions and brain neurotransmitters levels.
②At same time, the research mode of'Syndromes are the core while diseases are the complement' has been established which will play a role of demonstration effect in the future study of'Rigid-Gentle Syndrome Differentiation'.
③This study also could set up target indexes for diagnosis, effectiveness evaluation, screening effective drugs and their mechanisms of psychosomatic diseases from the aspects of cerebral cortex functions and brain neurotransmitters levels.
④This study indicates that negative stimuli of psycho-social factors can affect cerebral function, which causes organic disorders or process of pathologic physiology. This study provides the brain electrophysiological evidence for the TCM psychosomatic medicine theory "If the mentality is normal, the organs will function normally. This is the fundamental principle to keep good health and a long life" and "If the mentality is abnormal, it is very dangerous to the twelve organs including itself."
⑤This study also provides modern scientific data for basic researches of TCM syndrome from the EEG signals.
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