中文摘要
抑郁症发病机制与TRP-KYN通路受肠道菌群调节及其代谢影响神经可塑性密切相关;结合前期加味温胆汤可显著改善抑郁症患者情绪及胃肠道症状,以及调节胞内信号转导通路改变海马神经元萎缩、再生的机制研究,启示:加味温胆汤治疗抑郁症情绪、胃肠动力障碍的作用机制可能与调节肠道菌群影响TRP-KYN通路代谢改变神经可塑性有关。本项目采用慢性应激抑郁模型,通过:观测情绪、胃肠动力及相关脑-胃肠组织病理形态变化;以抗生素干预肠道菌群稳态,用16SrRNA测序、ERIC_PCR指纹图谱技术等研究肠道菌群变化;以抑制剂阻断TRP-KYN通路神经保护/毒性代谢途径,研究该通路变化对神经可塑性的影响,综合分析,揭示肠道菌群影响TRP-KYN通路改变神经可塑性在抑郁症情绪、胃肠动力障碍发病机制及加味温胆汤整体调节中的作用及其相互关系,以期为加味温胆汤有效临床实践提供新的科学依据,为抑郁症发病机制研究开辟新途径。
英文摘要
The pathogenesis of depression is closely related to intestinal flora regulating TRP - KYN pathway and TRP - KYN pathway metabolic changes affect neuroplasticity, In light of effects on ameliorating emotion and gastrointestinal symptoms in depression significantly, and mechanism of affecting intracellular signal transduction pathway to alter atrophy and regeneration of hippocampal neuron, which is well recognized about JiaWeiWendan Decoction in our previous research, We get the enlightenment:The mechanism of JiaWeiWendan Decoction’s therapeutic effects on ameliorating emotion and gastrointestinal symptoms in depression might involve with regulating intestinal flora to influence TRP-KYN pathway and then to affect neuroplasticity. Chronic stress induced depression model were adopted in this research, and including:Observations on changes of emotion, intestinal mobility and pathomorphological changes of brain-gastrointestinal tissue; Change Steady state of intestinal flora with antibiotics,and study the change of intestinal flora via 16SrRNA sequencing, ERIC_PCR fingerprint spectrum; Using inhibitors block the TRP - KYN pathway neural protection and toxicity of metabolic pathways to study the effect of the channel changes on neural plasticitystudy,With the comprehensive analysis to uncover the influence of intestinal flora regulating TRP - KYN pathway to change neural plasticity in the pathogenesis of emotion and gastrointestinal dysfunction in depression and the overall adjustment function of Jiawei wendan decoction and their mutual relations,it hopes to provide new scientific basis for JiaWeiWendan Decoction in clinical practice, and to to open up new approaches for studying pathogenesis of depression in the future.
