基于雌激素介导的ERK1/2信号转导通路研究补虚化瘀法治疗产后抑郁的作用机制

Tonify deficiency and remove blood stasis is the effective treatment of postpartum depression. Preliminary studies confirmed that the tonify deficiency and remove blood stasis therapeutic method have effective treatment on postpartum depression. However, what is the effective mechanism? Based on this question, our group make the postpartum depression rat model as the object of study, tonify deficiency and remove blood stasis prescription chanshu granule as the interventions, ERK1 / 2 signaling pathway as pointcut,closely around with the research hypothesis "whether the mechanism of tonify deficiency and remove blood stasis prescription could alleviate depression is through adjusting the level of estrogen and raised the ERK1 / 2 signaling transduction pathway?" We intend to intervene the postmartum depression rat model by Chinese medicine chanshu granules, western medicine sertraline, estradiol benzoate,and then detect serum estrogen levels, neurotrophic factor and the key points on ERK1 / 2 signaling pathway such as ERK1 and so on, under the help of classic detection technology such as Western blotting, immunohistochemical. Then to analysis relevant laboratory data under the help of advanced statistical analysis method. Reveal the mechanism and scientific connotation of tonify deficiency and remove blood stasis therapeutic method treat postpartum depression ,and support objective experimental basis for the Chinese medicine treat postpartum depression,s clinical application , and finally provided new ideas and new methods for the treatment of female estrogen-related diseases under the guidance of Chinese medicine theory.

补虚化瘀法是传统中医治疗产后抑郁的治疗大法。临床研究证实补虚化瘀法治疗产后抑郁安全有效。但其有效的作用机制是什么？基于此，本课题以产后抑郁模型大鼠为研究对象，以补虚化瘀方药产舒颗粒为干预手段，以在产后抑郁发病因素中起关键作用的雌激素及ERK1/2信号转导通路为切入点，密切围绕"对雌激素介导的ERK1/2信号转导通路的调节是补虚化瘀法治疗产后抑郁的作用机制？"这一研究假说，运用经典的蛋白印迹、免疫组化等检测技术，分别检测中药产舒颗粒、西药舍曲林、苯甲酸雌二醇三种干预手段下血清雌激素水平、神经营养因子及ERK1等ERK1/2信号转导通路的关键指标，运用先进统计分析方法将相关实验室数据进行分析，揭示传统中医药理论指导下的"补虚化瘀"法治疗产后抑郁的作用机制和科学内涵，为中医药治疗产后抑郁的临床应用提供客观实验依据，为中医药理论指导下女性"雌激素"相关疾病的研究提供可供参考的新思路和新方法。

多虚多瘀是产后抑郁的基本病机，临床采用补虚化瘀法治疗产后抑郁疗效确切，但作用机制不清。本课题以产后抑郁模型大鼠为研究对象，以补虚化瘀方药产舒颗粒为干预手段，以在产后抑郁发病因素中起关键作用的雌激素及ERK1/2 信号转导通路为切入点，运用经典的蛋白印迹、免疫组化等检测技术，分别检测中药产舒颗粒、西药干预手段下血清雌激素水平、神经营养因子及 ERK1等 ERK1/2信号转导通路的关键指标，运用先进统计分析方法将相关实验室数据进行分析，结果表明补虚化瘀方产舒颗粒（参归仁合剂）可提升产后抑郁大鼠血清雌二醇水平，补虚化瘀方产舒颗粒治疗产后抑郁可能通过提高雌激素及其受体水平从而促进BDNF与TRKB结合后激活ERK1/2信号转导通路，磷酸化MEK、ERK1/2、RSK1，进而磷酸化CREB发挥抗抑郁作用。揭示了“补虚化瘀法-雌激素—ERK1/2 信号转导通路-产后抑郁”的相关性，揭示了传统中医药理论指导下的“补虚化瘀”法治疗产后抑郁的作用机制和科学内涵，为中医药治疗产后抑郁的临床应用提供了客观实验依据。