基于液相色谱-质谱联用技术探讨愈癫汤对精神分裂症大鼠神经递质含量的影响  

Study on the effect of Yudian Decoction on neurotransmitter content in schizophrenic rats based on LC-MS/MS

作　　者：白冰 柴剑波[4,5] 王万宇 赵永厚 BAI Bing;CHAI Jianbo;WANG Wanyu;ZHAO Yonghou(Postdoctoral Research Station of Heilongjiang Mental Hospital, Harbin 150036, Heilongjiang, China;Postdoctoral Station of Integrated Traditional Chinese and Western Medicine of Fudan University,Shanghai 200433, China;Tongde Hospital of Zhejiang Province, Hangzhou 311100, Zhejiang, China;Heilongjiang Mental Hospital,Harbin 150036, Heilongjiang, China;Heilongjiang Provincial Mental Psychology Health Center Harbin, 150036, Heilongjiang, China;Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang, China)

机构地区：[1]黑龙江神志医院博士后科研工作站,黑龙江哈尔滨150036 [2]复旦大学中西医结合博士后流动站,上海200433 [3]浙江省立同德医院,浙江杭州311100 [4]黑龙江神志医院,黑龙江哈尔滨150036 [5]黑龙江省精神心理卫生研究中心,黑龙江哈尔滨150036 [6]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《现代中西医结合杂志》2021年第30期3317-3321,共5页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金资助项目(81873299,81973747);黑龙江省博士后科学基金资助项目(LBH-Z19095)。

摘　　要：目的基于液相色谱-质谱联用(LC-MS/MS)技术观察愈癫汤对精神分裂症大神经递质含量的影响,探讨愈癫汤治疗精神分裂症的分子作用机制。方法选择孕期17 d时腹腔注射甲基氧化偶氮甲醇醋酸盐(MAM)建立精神分裂症感觉运动门控障碍大鼠所生雄性子鼠30只,随机分为模型组、愈癫汤组和利培酮组,每组10只。另选择健康大鼠所生健康雄性子鼠10只作为正常组。子鼠5周龄时,愈癫汤组给予愈癫汤2.3 g/kg灌胃,利培酮组给予利培酮混浊液0.36 mg/kg灌胃,正常组和模型组给予等量蒸馏水灌胃,均连续灌胃3周。干预结束后处死各组子鼠,应用LC-MS/MS技检测纹状体组织中多巴胺(DA)及其代谢产物3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)和海马组织中谷氨酸(Glu)、γ-氨基丁酸(GABA)、天冬氨酸(ASP)的含量。结果与正常组比较,模型组纹状体组织中DA、HVA、DOPAC含量和海马组织中GABA含量均明显升高(P均<0.05),海马组织中Glu和ASP含量均明显降低(P均<0.05);与模型组比较,愈癫汤组、利培酮组纹状体组织中DA、HVA、DOPAC含量和利培酮组海马组织中GABA含量均明显降低(P均<0.05),海马组织中Glu和ASP含量均明显升高(P均<0.05);愈癫汤组纹状体组织中DA、HVA含量明显低于利培酮组(P均<0.05),海马组织中Glu含量明显高于利培酮组(P<0.05)。结论愈癫汤可能通过Glu-GABA-DA神经递质网络,调控共同神经环路中Glu、GABA、DA的功能活动和递质释放而发挥治疗精神分裂症的作用。Objective It is to observe the effect of Yudian Decoction on the content of neurotransmitter in the rats with schizophrenia based on the technique of liquid chromatography-mass spectrometry(LC-MS/MS),and to explore the molecular mechanism of Yudian Decoction in the treatment of schizophrenia.Methods Thirty male offspring born from the rats with schizophrenia sensorimotor gated disorder which were established by intraperitoneal injection of methyl azoxy methanol acetate(MAM)on the 17th day of pregnancy were selected and randomly divided into model group,Yudian Decoction group and risperidone group,10 animals in each group.In addition,10 healthy male offspring born from healthy rats were selected as the normal group.When the children were 5 weeks old,the Yudian Decoction group was given Yudian Decoction 2.3 g/kg by gavage,the risperidone group was given risperidone turbid solution 0.36 mg/kg by gavage,and the normal group and model group were given the same amount of distilled water by gavage,all the groups were treatment by intragastric administration for 3 weeks.After the treatment,the rats of each group were sacrificed,and the contents of dopamine(DA)and its metabolites 3,4-dihydroxyphenylacetic acid(DOPAC),homovanillic acid(HVA)in striatum tissue and the content of glutamic acid(Glu),γ-aminobutyric acid(GABA)and aspartic acid(ASP)in hippocampal tissue were detected by LC-MS/MS technology.Results Compared with the normal group,the content of DA,HVA,DOPAC in the striatum tissue and the content of GABA in the hippocampus of the model group were significantly increased(all P<0.05),and the content of Glu and ASP in the hippocampus were significantly decreased(all P<0.05);Compared with the model group,the contents of DA,HVA,DOPAC in the striatum tissue of the Yudian Decoction group and the risperidone group and the GABA content in the hippocampus of the risperidone group were significantly reduced(all P<0.05),the contents of Glu and ASP in the hippocampus were significantly increased(both P<0.05);the content of DA a

关 键 词：愈癫汤 精神分裂症 液相色谱-质谱联用 Glu-GABA-DA神经递质网络 

分 类 号：R-332[医药卫生]