基于cAMP-CREB-BDNF信号通路探讨交泰丸抗抑郁的作用机制

Antidepressant mechanism of Jiaotai pill based on cAMP-CREB-BDNF signaling pathway

关键词:  抑郁症  交泰丸  CUMS  cAMP-CREB-BDNF信号通路

Key words:  Jiaotai pill  depression  CUMS  cAMP-CREB-BDNF signal pathway

摘要:

[目的] 基于cAMP-CREB-BDNF信号通路探讨交泰丸抗抑郁作用机制。[方法] 采用慢性温和不可预知性应激刺激建立大鼠抑郁症模型。酶联免疫吸附实验（ELISA法）检测大鼠海马组织中环磷酸腺苷（cAMP）、磷酸化环磷腺苷效应元件结合蛋白（p-CREB）、脑源性神经营养因子（BDNF）的含量和磷酸二酯酶-4（PDE4）的活性以及血浆中cAMP含量的变化，逆转录PCR法（RT-PCR）测定海马、皮质中的BDNF mRNA的含量。免疫组织化学分析大鼠海马组织CA1和CA3区中p-CREB阳性细胞的表达数量变化。[结果] 与空白组相比，模型组的大鼠血浆及海马中cAMP含量明显降低，海马组织中CREB、BDNF含量降低，海马组织中PDE4活性增强，大鼠海马、皮质和下丘脑中BDNF mRNA表达含量减少，交泰丸逆转了以上改变。[结论] 交泰丸可以通过调节cAMP-CREB-BDNF信号通路发挥抗抑郁作用。

Abstract:

[Objective] The antidepressant mechanism of Jiaotai pill was discussed based on cAMP-CREB-BDNF signal pathway.[Methods] The rat model of depression was established by chronic mild unpredictable stress stimulation. Enzyme linked immunosorbent assay (ELISA) was used to detect the content of cyclic adenosine monophosphate (cAMP), phosphorylated cAMP-response element binding protein (p-CREB), brain derived neurotrophic factor (BDNF) and activity of phosphodiesterase (PDE4) in the hippocampus of rats, and the content of cAMP in plasma of rats. The content of BDNF mRNA in the hippocampus and cortex was measured by reverse transcriptase PCR (RT-PCR). The expression of P-CREB positive cells in the CA1 and CA3 regions of the hippocampus of rats was analyzed by immunohistochemistry.[Results] Compared with the blank group, the content of cAMP in rat plasma and hippocampus was significantly decreased, the content of CREB and BDNF in the hippocampus decreased, PDE4 activity in the hippocampus is enhanced and the expression of BDNF mRNA in the hippocampus, cortex and hypothalamus of rats decreased in model group. Jiaotai pills and positive drugs reversed the above changes.[Conclusion] Jiaotai pill can achieve antidepressant effect by regulating the cAMP-CREB-BDNF signaling pathway.