中文摘要
抑郁症发生与海马神经元再生障碍密切相关,cAMP-PKA-CREB信号通路是调控神经元再生的关键环节,也是抗抑郁治疗的重要靶点。在前期大量理论与临床研究的基础上,我们构建了抑郁症“阳郁神颓”创新的病机理论体系,并基于该病机理论创制了药效显著的“重大新药”候选药物—强志方,在初步药效与作用机制研究的基础上,提出了“抑郁症‘阳郁神颓’病机与神经细胞内信号通路对海马神经元再生调控相关”的假说。为进一步揭示该假说的科学内涵,研究以神经元再生与保护为切入点,采用经典的抑郁模型大鼠,从旷场实验、强迫游泳实验等行为学角度观察强志方抗抑郁作用,运用免疫组化等方法研究强志方对cAMP-PKA-CREB信号通路上的关键蛋白PKA、CREB表达及对海马神经发生的影响,明确强志方抗抑郁作用的生物学机制与作用靶点。研究不仅丰富发展了抑郁症创新的病机理论体系,有效指导临床实践,也为创新药物研发提供科学依据。
英文摘要
Depression is closely related to the disorder of hippocampal neurogenesis.The cAMP-PKA-CREB signaling pathway is key to regulate neuron regeneration ,and it is also an important target of antidepression.Based on the plenty of previous theoretical and clinical researches,we construct a new theoretical system of “yang yu shen tui”(yang qi stagnation leading to spirit deficiency)pathogenesis,based on which,we invent an effective formula called “QiangZhiFang” which is a candidate of “Significant New Medication”, On the basis of the preliminary efficacy and mechanism researches ,we reveal the mechanism of the antidepressant “QiangZhiFang” and propose the hypothesis about the relation between “yang yu shen tui”and “the signaling pathway in nerve cells which affects the regulation and the control of regeneration of hippocampal neurons”. In order to reveal the scientific connotation of the hypothesis, the research on nerve regeneration and protection is adopted as an entry point, by using the classic depression model rats,observing the anti-depression of “QiangZhiFang” from the view of behavioristics such as open field tests and forced swimming tests. We apply the method of Immunohistochemistry to study the effect of QiangZhiFang on the expression of key protein PKA and CREB on the cAMP-PKA-CREB signaling pathway, and on the hippocampal neurogenesis, figuring out the biological mechanism and targets of QiangZhiFang’s anti-depression effect. The study will not only enrich the innovation of pathogenesis theoretical system of depression, but also will guide the clinical practice effectively, and provide scientific basis for inventing new drugs .
