疏肝理脾类方调控色氨酸代谢的抗抑郁作用机制及共性药效物质  

Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances

作　　者：丛梦雨 梁晓霞 陈丰连[1] 曹骋[1] 王术玲[1] CONG Meng-yu;LIANG Xiao-xia;CHEN Feng-lian;CAO Cheng;WANG Shu-ling(Guangzhou University of Chinese Medicine,Guangzhou 510000,China;Jimo District Qingdao Hospital of Traditional Chinese Medicine,Qingdao 266000,China)

机构地区：[1]广州中医药大学,广东广州510000 [2]青岛市即墨区中医医院,山东青岛266000

出　　处：《中国中药杂志》2021年第14期3633-3642,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(817741932);广东省自然科学基金项目(2017A030313716);广州市科技计划项目(201707010443)。

摘　　要：探究疏肝理脾类方通过调控色氨酸代谢的抗抑郁作用机制,并找出其共性的药效物质。运用超高效液相色谱飞行时间质谱(UPLC-Q-TOF-MS)技术建立疏肝理脾类方的指纹图谱,鉴定出其中124种成分;三联一复合应激法复制抑郁小鼠模型,分组给药柴胡疏肝散、四逆散、逍遥散。与模型组相比,各给药组体质量、糖水偏好和自主活动行为方面均有改善作用,其中柴胡疏肝散作用优于四逆散和逍遥散;三重四极杆液质联用法测定血、肝、脑和结肠组织等中5-羟色胺(5-HT)、犬尿氨酸(KYN)、色氨酸(TRP)的含量和肝中色氨酸-2,3-双加氧酶(TDO)活性,采用Western blot和RT-PCR法分别检测TDO酶蛋白和基因表达,发现3种方药不同程度升高5-HT/KYN比例,减小KYN/TRP的比例,降低肝脏中TDO酶表达和酶活性,对色氨酸代谢调节作用的大小顺序为柴胡疏肝散>四逆散>逍遥散;通过灰色关联度分析疏肝理脾类方指纹图谱中色谱峰与色氨酸代谢药效指标的相关性,找到其中与色氨酸代谢关联度最高的化学成分主要来自白芍、陈皮、枳实、枳壳;利用UPLC-Q-TOFMS对这些成分在血浆内的移行情况进行研究,共鉴定出其中18种原型成分和36种代谢产物。表明柴胡疏肝散、四逆散、逍遥散可通过降低肝中TDO酶表达、调控色氨酸代谢起到抗抑郁作用,方中白芍以及芸香科柑橘属的陈皮、枳实、枳壳所含成分为其共性药效物质,对调节色氨酸代谢有重要作用。This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances.UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified.The depressed mouse model was replicated by triple-one multiple stress method.Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice.The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved.Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder.LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine(5-HT),kynurenine(KYN)and tryptophan(TPP)in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver.Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively.It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver.The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder.In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis.The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus.UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Li

关 键 词：抑郁症 色氨酸代谢 柴胡疏肝散 四逆散 逍遥散 

分 类 号：R285.5[医药卫生—中药学]