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[摘要]
目的 基于cAMP-CREB-BDNF通路探讨柴胡-白芍药对抗抑郁的作用机制。方法 建立慢性温和不可预知应激(CUMS)大鼠抑郁模型,ELISA法测定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)和磷酸二酯酶抑制剂(PDE4)以及血浆中cAMP水平的变化,采用RT-PCR法测定海马、下丘脑和皮质中的BDNF mRNA的表达。结果 与模型组相比,阳性药组、柴胡-白芍药对给药组可以不同程度地逆转大鼠海马组织及血浆中cAMP水平和大鼠海马组织中p-CREB、BDNF水平的降低。同时阳性药组、柴胡-白芍药对给药组能够增加大鼠海马、皮质和下丘脑中BDNF mRNA的表达。结论 柴胡-白芍药对对CUMS大鼠模型具有明显的抗抑郁作用,并可以通过调节cAMP-CREB-BDNF通路而达到抗抑郁的作用。
[Key word]
[Abstract]
Objective To investigate the antidepressant effect of Bupleuri Radix and Paeoniae Alba Radix drug pair based on the cAMP-CREB-BDNF pathway. Methods The rat depression model was established by CUMS. The contents of cAMP, p-CREB, BDNF, and PDE4 in rat hippocampal and cAMP levels in rat plasma were determined by ELISA. The expression of BDNF mRNA in hippocampus, hypothalamus, and cortex were measured by RT-PCR. Results Compared with the model group, the positive drug group and Bupleuri Radix and Paeoniae Alba Radix drug pair can reverse the cAMP content in the hippocampus and plasma and the decreased contents of CREB and BDNF in the rat hippocampus. At the same time, the positive drug group, Bupleuri Radix, and Paeoniae Alba Radix can increase the expression of BDNF mRNA in hippocampus, cortex, and hypothalamus of rats. Conclusion The Bupleuri Radix and Paeoniae Alba Radix drug pair has obviously antidepressant effect on CUMS rat model, which can achieve antidepressant effect by regulating cAMP-CREB-BDNF pathway.
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[基金项目]
国家自然科学基金资助项目(81273893);天津市科技计划项目资助(13JCZDJC31600)