鉴于中医药治疗抑郁症的临床有效性,但有效机制不清,该研究试图从抑郁症的病因源头做起,在复杂系统下初探抑郁症的可能病因,为下一步中医药疗效评价研究奠定基础。通过采集120例抑郁症患者和40例健康人群脑电波,利用脑讯息搜索(SET,sear...鉴于中医药治疗抑郁症的临床有效性,但有效机制不清,该研究试图从抑郁症的病因源头做起,在复杂系统下初探抑郁症的可能病因,为下一步中医药疗效评价研究奠定基础。通过采集120例抑郁症患者和40例健康人群脑电波,利用脑讯息搜索(SET,search of encephalo-telex)系统分析抑郁症患者全脑及各脑区抑制性神经递质(INH)、五羟色胺(5-HT)、乙酰胆碱(ACH)、多巴胺(DA)、去甲肾上腺素(NE)、兴奋性神经递质(EXC)这6种神经递质的变化规律。结果显示:抑郁症组与健康组比较,各神经递质均值变化为①抑郁组全脑区DA降低(P<0.05),且双侧中央区,右颞区及右顶区DA降低较显著(P<0.01);②抑郁组右颞区5-HT升高(P<0.05);③抑郁组右中央、左顶区ACH降低(P<0.05),左后颞区ACH降低较显著(P<0.01)。神经递质拮抗对及神经递质间相关性研究①3对神经递质拮抗对5-HT与DA,Ach与NE,INH与EXC在健康组和抑郁组2组均表现为中或强负相关性。5-HT与DA之间,除健康组右后颞区为弱负相关外,其余各区及全脑均表现出强负相关性(健康组除外右后颞区,|r|范围为[0.82,0.92],P<0.01)/(抑郁组,|r|范围为[0.88,0.94],P<0.01);Ach与NE间在全脑及各脑区体现出中负相关性(健康组,|r|范围为[0.39,0.76],P<0.01或P<0.05)/(抑郁组,|r|范围为[0.56,0.64],P<0.01);INH与EXC间体现出中强负相关性(健康组,|r|范围为[0.57,0.80],P<0.01)/(抑郁组,|r|范围为[0.68,0.78],P<0.01)。②非拮抗对的两两递质组间,5-HT与EXC间,或Ach与INH间,或DA与INH间在大脑各区均呈现弱负相关趋势。5-HT与EXC间表现出弱负相关性(健康组,在脑右中央、左顶、双前颞和右后颞区|r|范围为[0.25,0.50],P<0.01或P<0.05)/(抑郁组,在全脑、双顶、双枕、右前颞、双后颞、左中央、左额区表现出弱负相关性(|r|范围为[0.18,0.37],P<0.01或P<0.05);Ach与INH间表现出弱负相关性(健康组,在脑双额、左顶、左前颞、右后颞区|r|�展开更多
Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-a...Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.展开更多
文摘鉴于中医药治疗抑郁症的临床有效性,但有效机制不清,该研究试图从抑郁症的病因源头做起,在复杂系统下初探抑郁症的可能病因,为下一步中医药疗效评价研究奠定基础。通过采集120例抑郁症患者和40例健康人群脑电波,利用脑讯息搜索(SET,search of encephalo-telex)系统分析抑郁症患者全脑及各脑区抑制性神经递质(INH)、五羟色胺(5-HT)、乙酰胆碱(ACH)、多巴胺(DA)、去甲肾上腺素(NE)、兴奋性神经递质(EXC)这6种神经递质的变化规律。结果显示:抑郁症组与健康组比较,各神经递质均值变化为①抑郁组全脑区DA降低(P<0.05),且双侧中央区,右颞区及右顶区DA降低较显著(P<0.01);②抑郁组右颞区5-HT升高(P<0.05);③抑郁组右中央、左顶区ACH降低(P<0.05),左后颞区ACH降低较显著(P<0.01)。神经递质拮抗对及神经递质间相关性研究①3对神经递质拮抗对5-HT与DA,Ach与NE,INH与EXC在健康组和抑郁组2组均表现为中或强负相关性。5-HT与DA之间,除健康组右后颞区为弱负相关外,其余各区及全脑均表现出强负相关性(健康组除外右后颞区,|r|范围为[0.82,0.92],P<0.01)/(抑郁组,|r|范围为[0.88,0.94],P<0.01);Ach与NE间在全脑及各脑区体现出中负相关性(健康组,|r|范围为[0.39,0.76],P<0.01或P<0.05)/(抑郁组,|r|范围为[0.56,0.64],P<0.01);INH与EXC间体现出中强负相关性(健康组,|r|范围为[0.57,0.80],P<0.01)/(抑郁组,|r|范围为[0.68,0.78],P<0.01)。②非拮抗对的两两递质组间,5-HT与EXC间,或Ach与INH间,或DA与INH间在大脑各区均呈现弱负相关趋势。5-HT与EXC间表现出弱负相关性(健康组,在脑右中央、左顶、双前颞和右后颞区|r|范围为[0.25,0.50],P<0.01或P<0.05)/(抑郁组,在全脑、双顶、双枕、右前颞、双后颞、左中央、左额区表现出弱负相关性(|r|范围为[0.18,0.37],P<0.01或P<0.05);Ach与INH间表现出弱负相关性(健康组,在脑双额、左顶、左前颞、右后颞区|r|�
基金supported by the Natural Science Foundation of State(Nos.81603289 and 81603251)the Base Program of the Joint Training Talents of Shanxi Province(No.2017JD01)the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No.201605D111004)
文摘Ziziphi Spinosae Semen(ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin(5-HT), glutamic acid(Glu),γ-aminobutyric acid(GABA),noradrenaline(NE) and dopamine(DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESIMS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring(MRM) and the procedure was completed in less than 10 min. The method showed a good linearity(R^2 >0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower(P < 0.01) in para-chlorophenylalanine(PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group(P < 0.01). Treatment with ZSS aqueous extract(4 or 8 g·kg^1·d^-1 for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.
