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基于亲水作用色谱-质谱联用技术和神经脂质组学的柴胡疏肝散抗脑卒中后抑郁的作用机制研究

基于亲水作用色谱-质谱联用技术和神经脂质组学的柴胡疏肝散抗脑卒中后抑郁的作用机制研究
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  • 批准号:81673889
  • 批准年度: 2016年
  • 学科分类:中医内科(H2708) |
  • 项目负责人:朱黎霞
  • 负责人职称:副主任医师
  • 依托单位:南方医科大学
  • 资助金额:57万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 脂质;组学;柴胡疏肝散;脑卒中;抑郁
  • 英文关键词:Hydrophilic interaction chromatography / mass spectrometry combining technique;Neurolipidomics;Chaih

项目摘要

中文摘要

脑卒中后抑郁(PSD)是临床多发病,柴胡疏肝散是治疗肝气郁结型PSD安全、有效的经典名方。本课题拟结合动物实验和临床研究挖掘柴胡疏肝散抗PSD的作用机制。. 以柴胡疏肝散水煎液冻干粉给药,采用“颈外动脉注射微球加中长期饲养法”复制PSD大鼠模型。脑微透析技术结合高效液相色谱电喷雾串联质谱仪实现PSD大鼠海马神经递质和柴胡疏肝散入脑成分动态采样、精确测定,建立PK-PD相关性模型。在优化色谱、质谱条件及神经脂质组前处理基础上,建立基于UPLC-Q-TOF/MS的神经脂质组学亲水作用色谱-质谱联用技术平台,进行柴胡疏肝散对PSD模型大鼠脑区、脑脊液、肝气郁结型PSD患者脑脊液的神经脂质组学研究,结合生物信息学和多元统计揭示神经脂质代谢网络信号分子在PSD发病机制的作用,阐述柴胡疏肝散抗PSD的神经脂质组学作用机制和科学内涵,为进一步开发研究和提高临床疗效提供科学依据。

英文摘要

Post Stroke Depression (PSD) is clinical frequently occurring disease. Chaihu-Shu-Gan-San is classical prescription on the PSD treatment of liver Qi type stagnation syndrome which the safety and efficiency is widely recognized. This paper intends to combine the animal experiment and clinical research on mining the action mechanism of Chaihu-Shu-Gan-San against PSD.The lyophilized powder of Chaihu-Shu-Gan-San water decoction would been prepared as administration form. The PSD rat model would been established by external carotid artery injection of microspheres and long-term feeding. The neurotransmitters and components coming from Chaihu-Shu-Gan-San in rat hippocampus using cerebral microdialysis sampling technology combined with high-performance liquid phase chromatography electrospray tandem mass spectrometry could been dynamic sampled and accurately determinated to establish the PK-PD correlation model. The neurolipidomics test platform would been established using hydrophilic interaction chromatography - mass spectrometry techniques based on the optimization of chromatographic and mass spectrometric conditions and biological samples pretreatment using ultra performance liquid chromatography flight time mass spectrometry instrument as the analysis instrument. The neurolipidomics research of PSD model rat brain region, cerebrospinal fluid from both PSD rat and patients with liver Qi stagnation syndrome which treated Chaihu-Shu-Gan-San, would been carried out. The role of neurolipidome metabolic network signal molecules in the pathogenesis of PSD could been revealed combining biological information and multivariate statistics. This action mechanism and scientific connotation of Chaihu-Shu-Gan-San could been illuminated based on neurolipidomics against PSD.This study is beneficial to provide scientific basis for further research and development and improvement of clinical curative effect of Chaihu-Shu-Gan-San.

评估说明

    国家自然科学基金项目“基于亲水作用色谱-质谱联用技术和神经脂质组学的柴胡疏肝散抗脑卒中后抑郁的作用机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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