【摘要】 目的:探究汉黄芩素（Wog）调节AMP活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对抑郁症大鼠抑郁样行为的改善作用及机制。方法:建立抑郁症大鼠模型，实验分为对照组（Control组）、模型组（Model组）、汉黄芩素低、中、高剂量组(Wog-L、Wog-M、Wog-H组，7mg·kg^-1·d^-1、14mg·kg^-1·d^-1、28mg·kg^-1·d^-1 Wog)和汉黄芩素高剂量+AMPK抑制剂Compound C组(Wog-H+Compound C组，28mg·kg^-1·d^-1 Wog+0.14mg·kg^-1·d^-1 Compound C)。采用蔗糖偏好、旷场实验和强制游泳实验观察大鼠抑郁样行为；ELISA测定DA、5-HT水平；透射电镜观察海马组织超微结构及自噬变化；Nissl染色观察海马CA1区神经元形态变化；免疫组化检测BDNF表达；Western blot检测AMPK、p-AMPK、mTOR、p-mTOR、P62和Beclin-1表达。结果:与Control组相比，Model组神经元排列稀疏，伴有神经元丢失及炎性细胞浸润，细胞间隙增宽，尼氏体颗粒减少，着色变浅，线粒体及神经元胞质肿胀严重，线粒体边界模糊，内质网和高尔基体扩张，自噬囊泡数量减少，糖水偏好、站立时间、移动距离、DA和5-HT水平、BDNF光密度值及Beclin-1和p-AMPK/AMPK表达显著减少，静止时间及P62和p-mTOR/mTOR表达显著增加（P<0.05）;与Model组相比，Wog-L组、Wog-M组和Wog-H组神经元形态明显改善，糖水偏好、站立时间、移动距离、DA和5-HT水平、BDNF光密度值及Beclin-1和p-AMPK/AMPK表达显著增加，静止时间及P62和p-mTOR/mTOR表达显著减少（P<0.05）。Compound C逆转了汉黄芩素对抑郁症大鼠的改善作用（P<0.05）。结论:汉黄芩素能改善抑郁症大鼠抑郁样行为，其机制可能与调控AMPK/mTOR信号通路，增强自噬有关。更多还原

【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.更多还原