逍遥散及其组方抗抑郁作用及机制分析--对大鼠海马神经元的保护及bdnf trkb表达的影响-antidepressant effect and mechanism analysis of xiaoyao powder and its prescription - effect on protection of hippocampal neurons and expression of bdnf trkb in rats.docxVIP

成都中医药大学硕士毕业论文  PAGE 3 中文摘要 逍遥散源于宋《太平惠民和剂局方》，由柴胡、当归、白芍、茯苓、白术、 薄荷、甘草、煨生姜组成，具有疏肝健脾、理气养血之功，主治肝郁血虚脾弱之 证。现代药理研究与临床应用均证实其具有良好的抗抑郁作用，但对其组方原理 和作用机制仍知之甚少。 本课题在传统中医药理论指导下，采用行为绝望抑郁小鼠模型和大鼠海马神 经元体外培养实验方法，观察、探讨逍遥散的抗抑郁作用及其组方规律，并从含 药血清和脑脊液体外影响大鼠海马神经元谷氨酸神经毒性和 BDNF、TrkB mRNA 表达的角度，对其作用机制进行研究。结果表明： 1. 逍遥散在小鼠 TST 和 FST 中表现出显著的抗抑郁样作用，方中君药—— 柴胡，臣药——当归白芍药对是其发挥抗抑郁样作用的主要组方药物。 2. 含逍遥散、柴胡、当归+白芍药对的大鼠血清及家兔脑脊液，体外对谷氨 酸所致的大鼠海马神经元神经毒性具有显著保护作用，并初步提示其作用有赖于 BDNF-TrkB 通路。 3. 含逍遥散脑脊液能使体外培养的大鼠海马神经元 BDNF 与 TrkB mRNA 的表达增加，含当归+白芍药对脑脊液使 BDNF mRNA 表达增加，含柴胡脑脊液 对 TrkB mRNA 的表达有提高作用。 4. 通过比较含药血清与含药脑脊液的体外实验结果，认为含药脑脊液的成 分相对简单，更加接近神经细胞的在体环境，与含药血清相比更适合用于作用于 中枢神经系统的中药的体外机制研究。 综上，逍遥散具有抗抑郁作用，方中柴胡、当归、白芍发挥至关重要的作用； 其作用与影响 BDNF-TrkB 途径有关。此外，含药脑脊液比含药血清更适合于作 用于中枢神经系统的中药体外机制研究。 关键词：逍遥散 组方 抗抑郁 机制 BDNF TrkB  英文摘要 Abstract Xiaoyao Powder (XYS), which originated from official medical workings of Taiping Huimin Heji Jufang in Song Dynasty, is used to treat depression of Liver-Qi and insufficiency of Spleen-Qi. It is composed of 8 Chinese herbs: Bupleurum scorzonerifolium Willd (Bs), Angelicae sinensis(Oliv) Diels and Paeoniae lactiflora Pall (AP), Poria cocos(Schw) Wolf and Atractylodis macrocephala Koidz (AtP), Glycyrrhiza uralensis Fisch, Menthae haplocalyx Briq, etc. Anti-depression effect of XYS was certified in early research in pharmacology and in clinic. However，the mechanism of its anti-depression and the principle of its components is not clear. Based on the T.C.M theory, we investigated the anti-depression effect and its mechanism of XYS and its main utility components. The results showed as follows: XYS and its main utility components, Bs and AP, exhibited obvious antidepressant-like effect by FST (forced swimming test) and TST (tail suspension test) in mice. Rat’s serum and rabbit’s CSF, which contained XYS and its main utility components, exhibited the neuroprotection effects on neurotoxicity induced by glutamate acid in cultured hippocampus neurons, which probably through BDNF-TrkB pathway. Rabbit’s CSF contained