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.
