基于雌激素介导的PI3K/Akt/mTOR信号通路研究补虚化瘀法治疗产后抑郁的作用机制

The multiple deficiency and blood stasis is the basic pathogenesis on postpartum depression. The clinical application of the tonify deficiency and remove blood stasis therapeutic method is effective in the treatment on postpartum depression, but the mechanism is not clear. The research group’s previous studies found that Chinese medicine chanshu granule, the prescription of tonify deficiency and remove blood stasis therapeutic method could produce anti-postpartum depression by activating the ERK1/2 signaling pathway. The foreign latest study found that the PI3K/Akt/mTOR signaling pathway also played an important role in the morbidity on depression. BDNF is the common upper reaches of the ERK1/2 pathway and the PI3K/Akt/mTOR pathway. Therefore, the research group puts forward the hypothesis that Chinese medicine chanshu granule, the prescription of tonify deficiency and remove blood stasis therapeutic method can regulate the PI3K/Akt/mTOR pathway in the treatment on postpartum depression.The postpartum depression model rats were used as the research object, Chinese medicine chanshu granule was used as the intervention means in this research. Under the help of detection technologies, such as RT-PCR, Western blotting and TUNEL,we are aim to detect the differences in expression of key node effector molecules and target molecules in PI3K/Akt/mTOR pathway respectively, and use the specific inhibition to verify. The research results have important significance to reveal the mechanism and scientific connotation of the treatment on postpartum depression with the method of tonify deficiency and remove blood stasis therapeutic, and also provide a new idea and method for the research of female diseases related low levels of estrogen under the guidance of the theory of traditional Chinese medicine.

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。课题组前期研究发现，补虚化瘀方药产舒颗粒可通过BDNF激活ERK1/2通路产生抗抑郁作用。国外最新研究发现PI3K/Akt/mTOR信号通路在抑郁症发病中同样具有重要作用。BDNF为ERK1/2通路和PI3K/Akt/mTOR通路的共同上游，因此，课题组提出补虚化瘀方药产舒颗粒可通过调控PI3K/Akt/mTOR通路治疗产后抑郁的假说。本研究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，运用RT-PCR、Western blotting、TUNEL等检测技术，分别检测PI3K/Akt/mTOR通路关键节点效应分子和靶分子的表达差异，并采用特异性抑制进行验证，研究结果对揭示补虚化瘀法治疗产后抑郁的作用机制和科学内涵具有重要意义，也为中医药理论指导下女性“低雌激素”相关疾病的研究提供新思路。

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。课题组前期研究发现，补虚化瘀方药产舒颗粒可通过BDNF激活ERK1/2通路产生抗抑郁作用。国外最新研究发现PI3K/Akt/mTOR信号通路在抑郁症发病中同样具有重要作用。BDNF为ERK1/2通路和PI3K/Akt/mTOR通路的共同上游，因此，课题组提出补虚化瘀方药产舒颗粒可通过调控PI3K/Akt/mTOR通路治疗产后抑郁的假说。本研究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，运用RT-PCR、Western blotting、TUNEL等检测技术，分别检测PI3K/Akt/mTOR通路关键节点效应分子和靶分子的表达差异，并采用特异性抑制剂进行验证，运用先进统计学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）可维持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维持雌激素及其受体水平从而促进BDNF与TrkB结合后激活PI3K/Akt/mTOR信号转导通路，磷酸化Akt、mTOR，进而磷酸化CREB发挥抗抑郁作用。实验研究结果对揭示补虚化瘀法治疗产后抑郁的作用机制和科学内涵具有重要意义，也为中医药理论指导下女性“低雌激素”相关疾病的研究提供新思路。