基于cAMP和cGMP信号转导通路探讨交泰丸抗抑郁的作用机制

Jiaotai pill was record in "Han shi yi tong" writed by Han Mao in Ming dynasty. The indication of Jiaotai pill (Rhizoma Coptidis and Cinnamon) was "imbalance between heart-yang and kidney-yin, severe palpitation and agrypnia". They were not only used to mainly treat insomnia, but also depression in clinical reports. The prophase study results of pharmacodynamics suggested that Jiaotai pill had antidepressant-like effect, but antidepressant-like effect mechanism of Jiaotai pill was not reported. In this study, Jiaotai pill (Rhizoma Coptidis: Cinnamon=10:1) as the object, our group would investigate the antidepressant-like effect mechanism of Jiaotai pill by the methods of HPLC-ECD,RT-PCR, ELISA,immunohistochemistry and so on. At the same time, the relevance of the targets in cAMP-PKA-CREB-BDNF signal pathway and NO-cGMP-PKG signal pathway, nervous and endocrine system was analyzed comprehensively in order to reveal the science connotation of integrated regulation of Han-Re compatibility of Jiaotai pill. Thus the study could provide the scientific basis for the antidepressant treatment with Jiaotai pill.

交泰丸出自明朝o韩懋《韩氏医通》，由黄连和肉桂两味药组成，主治"心肾不交，怔忡无寐"，临床主要用于治疗失眠，也有治疗抑郁症的报道。前期药效学研究结果表明交泰丸具有抗抑郁的作用，但交泰丸抗抑郁的作用机制尚未见文献报道。本项目以古方交泰丸（黄连与肉桂10:1）作为研究对象，采用HPLC-ECD、RT-PCR、ELISA和免疫组化等方法从cAMP-PKA-CREB-BDNF和NO-cGMP-PKG细胞信号转导通路、神经内分泌系统等角度，探讨交泰丸治疗抑郁症的作用机制，同时综合分析上述各项指标之间的关联性，揭示交泰丸寒热配伍整合调节的科学内涵，为交泰丸治疗抑郁症的临床应用提供科学依据。

交泰丸出自明朝•韩懋《韩氏医通》，由黄连和肉桂两味药以10:1 的比例组成，主治“心肾不交，怔忡无寐”。临床主要用于治疗失眠、更年期综合征等。本课题应用“双提法”对中药复方交泰丸进行了提取工艺的优化及改良，并分别从药效学、作用机制等方面对交泰丸的抗抑郁效果开展研究，最终确定了黄连与肉桂配伍的最佳剂量范围，明确了其抗抑郁作用。在研究过程中，以脑内单胺类神经递质、cAMP-PKA-CREB-BDNF 细胞信号转导通路、NO-cGMP-PKG细胞信号转导通路、内分泌系统等相关指标为主要检测对象，分析了各指标间的相关性，初步揭示了交泰丸治疗抑郁症的作用机制。主要对脑内单胺类神经递质及其相应受体，cAMP的含量，CREB磷酸化水平，BDNF的含量，PDE活性，cGMP含量，NO含量，NO合酶（包括iNOS、nNOS）基因mRNA，NMDA 受体亚单位NR1、NR2A和NR2B基因mRNA，Cort含量等指标进行了HPLC-ECD、ELISA、RT-PCR、免疫组织化学分析等方法的检测，初步确定了交泰丸的抗抑郁作用靶点和机制。. 该项目主要创新点是在药效学考量交泰丸抗抑郁作用的基础上，分别从脑内单胺类神经递质、cAMP-PKA-CREB-BDNF细胞信号转导通路、NO-cGMP-PKG细胞信号转导通路、内分泌系统等相关通路及指标进行检测，初步揭示了交泰丸抗抑郁的作用靶点和机制，分析了交泰丸寒热配伍整合调节的科学内涵，为黄连、肉桂配伍治疗抑郁症的临床应用提供了科学依据。