汉黄芩素调节AMPK/mTOR信号通路对抑郁症大鼠抑郁样行为的改善作用研究

doi:10.3969/j.issn.1006-6233.2024.09.08

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Abstract Objective: To investigate the improvement effect and mechanism of Wogonin (wog) on depression-like behavior in depression rats by regulating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway.Methods: A depression rat model was established, and the experiment was separated into control group, model group, low, medium, and high dose wogonin groups (Wog-L, Wog-M, Wog-H groups, 7mg·kg^-1·d^-1, 14mg·kg^-1·d^-1, 28mg·kg^-1·d^-1 Wog), and high-dose wogonin+AMPK inhibitor Compound C group (Wog-H+Compound C group, 28mg·kg^-1·d^-1 Wog+0.14mg·kg^-1·d^-1 Compound C). Sucrose preference, open field experiment, and forced swimming experiments were applied to observe depression-like behavior in rats; ELISA was applied to measure DA and 5-HT levels; transmission electron microscopy was applied to observe the ultrastructure and autophagy changes of hippocampal tissue; Nissl staining was applied to observe the morphological changes of neurons in the hippocampal CA1 region; immunohistochemistry was applied to detect the BDNF expression; Western blot was applied to detect the expression of AMPK, p-AMPK, mTOR, p-mTOR, P62, and Beclin-1. Results: Compared with the control group, the model group had sparse neuronal arrangement, accompanied by neuronal loss and inflammatory cell infiltration, widened cell gaps, reduced Nissl granules, lighter staining, severe swelling of mitochondria and neuronal cytoplasm, blurred mitochondrial boundaries, expansion of endoplasmic reticulum and Golgi apparatus, and reduced number of autophagic vesicles, the sugar preference, standing time, movement distance, the levels of DA and 5-HT, BDNF optical density values, and the expression of Beclin-1 and p-AMPK/AMPK were obviously reduced, the resting time and the expression of P62 and p-mTOR/mTOR were obviously increased (P<0.05). Compared with the model group, the morphology of neurons in WAG-L, WAG-M, and WAG-H groups was significantly improved, and the sugar water preference, standing time, moving distance, DA and 5-HT levels, BDNF optical density and Beclin-1 and p-AMPK/AMPK expression were significantly increased, the rest time and expression of P62 and P-MTOR /mTOR were significantly decreased (P<0.05). Compound C reversed the improvement effect of baicalin on depression in rats (P<0.05).Conclusion: Wogonin can improve depression-like behavior in rats with depression, and its mechanism may be related to regulating the AMPK/mTOR signaling pathway and enhancing autophagy.

Key words： Wogonin AMP-activated protein kinase/mammalian target of rapamycin signaling pathway Depression Depression-like behavior

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.09.08 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I9/1456

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