目的 探究脑心清片对抑郁及失眠动物药效及作用机制。方法 采用小鼠强迫游泳实验及小鼠悬尾实验观察脑心清片（0.25、0.50、1.00、2.00 g·kg^-1）对应激所致小鼠抑郁模型不动时间的影响。采用大鼠嗅球切除脑损伤抑郁模型，评价脑心清片（0.25、0.50、1.00 g·kg^-1）对糖水偏爱率、跳台实验逃避潜伏期的影响，ELISA法测定血清中促肾上腺皮质激素（ACTH）、皮质酮（CORT）水平，皮层中脑源性神经营养因子（BDNF）、5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）水平，海马中环磷酸腺苷（cAMP）水平； Western blotting法检测海马中蛋白激酶A（PKA）、磷酸化环磷腺苷效应元件结合蛋白（p-CREB）水平。采用小鼠延长戊巴比妥钠睡眠时间实验评价脑心清片（0.5、1.0、2.0 g·kg^-1）对入眠潜伏期及睡眠时间的影响。采用氯苯丙胺酸（PCPA）致大鼠失眠模型实验，ELISA法探究脑心清片（0.25、0.50、1.00 g·kg^-1）对血清ACTH水平和大脑中5-HT、NE、肾上腺素（E）、DA、γ-氨基丁酸（GABA）水平的影响。结果 在强迫游泳所致小鼠抑郁模型中，脑心清片0.25、0.50、1.00、2.00 g·kg^-1预防给予3 d使小鼠静止不动时间均显著减少（P＜0.05、0.01、0.001）；在悬尾所致小鼠抑郁模型中，脑心清片0.25、0.50、1.00、2.00 g·kg^-1预防给予3 d对小鼠静止不动时间未见显著影响。在大鼠嗅球切除模型中，脑心清片0.5、1.0 g·kg^-1给药14 d可以提高嗅球切除大鼠的糖水偏爱率（P＜0.05、0.01）； 1 g·kg^-1剂量显著提高皮层中5-HT（P＜0.05）及海马中cAMP、PKA含量（P＜0.05），皮层中BDNF及海马中pCREB含量亦有所提高；对血清中ACTH、CORT，皮层中DA、NE含量均无明显影响。在延长戊巴比妥钠睡眠时间实验中，脑心清片0.5、1.0、2.0 g·kg^-1预防给药3 d后，可缩短睡眠潜伏期（P＜0.001），脑心清片1、2 g·kg^-1预防给药3 d后，可延长睡眠时间（P＜0.05、0.01）。在PCPA致大鼠失眠模型实验中，脑心清片0.5、1.0 g·kg^-1治疗给药7 d后能显著降低血清中ACTH含量（P＜0.05、0.01），降低大脑NE含量（P＜0.05、0.001），脑心清片1 g·kg^-1治疗给药7 d后能提高大脑中5-HT含量（P＜0.05）。结论 脑心清片有明显抗抑郁及失眠作用，抗抑郁机制可能与抗应激、提高皮层中5-HT含量，激活海马中cAMP-PKA信号通路有关；抗失眠机制可能与降低大鼠血清ACTH含量、提高大脑5-HT含量及降低NE含量有关。

Objective To study effects and mechanisms of Naoxinqing Tablets on animals with insomnia or depression. Methods The effects of Naoxinqing Tablets (0.25, 0.50, 1.00, 2.00 g·kg^-1) on immobility time in mice with depression models induced by stress were observed through forced swimming test and tail suspension test in mice. The effects of Naoxinqing Tablets (0.2 5, 0.50, and 1.00 g·kg^-1) on sucrose preference rate and escape latency in the step-down test in rats with olfactory bulbectomy-induced brain injury depression models were evaluated. The levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in serum, brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in cortex, and cyclic adenosine monophosphate (cAMP) in hippocampus were determined by ELISA. The levels of protein kinase A (PKA) and phosphorylated cAMP response element binding protein (p-CREB) in hippocampus were detected by Western blotting. The effects of Naoxinqing Tablets (0.5, 1.0, and 2.0 g·kg^-1) on sleep latency and sleep time were evaluated by pentobarbital sodium-induced prolonged sleep test in mice. The effects of Naoxinqing Tablets (0.25, 0.50, and 1.00 g·kg^-1) on the levels of ACTH in serum and 5- HT, NE, epinephrine (E), DA, and γ-aminobutyric acid (GABA) in brain were investigated by ELISA in rats with insomnia models induced by p-chlorophenylalanine (PCPA). Results In the mice depression model induced by the forced swimming test, pretreatment with Naoxinqing tablets at doses of 0.25, 0.50, 1.00, and 2.00 g·kg^-1 for three days significantly reduced immobility time (P<0.05, 0.01, and 0.001) and ameliorated depressive-like behaviors. In the mice model of depression induced by the tail suspension test, pretreatment with Naoxinqing tablets at doses of 0.25, 0.50, 1.00, and 2.00 g·kg^-1 for three days did not significantly alter the immobility time of the mice. In the rat model of depression induced by olfactory bulbectomy, administration of Naoxinqing Tablets at doses of 0.5, and 1.0 g·kg^-1 for 14 days significantly elevated sucrose preference (P<0.05, and 0.01) and administration of Naoxinqing Tablets at doses of 1 g·kg^-1 for 14 days significantly increased 5-HT levels in the cortex (P<0.05), as well as cAMP and PKA levels in the hippocampus (P<0.05). An increase was also observed in the levels of BDNF and hippocampal pCREB. However, no significant effects were observed on serum ACTH and CORT levels, cortical DA, and NE. In the prolonged pentobarbital-induced sleep test, pretreatment with Naoxinqing Tablets at doses of 0.5, 1.0, and 2.0 g·kg^-1 for three days decreased sleep latency (P<0.001) and Naoxinqing Tablets at doses of 1, and 2 g·kg^-1 for three days extended sleep duration (P<0.05, and 0.01). In the PCPA-induced rat insomnia model, treatment with Naoxinqing Tablets at doses of 0.5, and 1.0 g·kg^-1 for seven days significantly lowered serum ACTH levels (P<0.05, and 0.01), reduced brain NE levels (P<0.05, and 0.001) and treatment with Naoxinqing tablets at doses of 1 g·kg^-1 for seven days significantly increased brain 5-HT content (P<0.05). Conclusion Naoxinqing Tablets have significant antidepressant and anti-insomnia effects. The antidepressant mechanism may be related to stress resistance, increased 5-HT content in the cortex, and activation of the cAMP-PKA signaling pathway in the hippocampus. The anti-insomnia mechanism may be related to decreased ACTH content in rat serum, increased brain 5-HT content, and decreased NE content.

R285.5

广州市科学技术协会青年科技人才托举工程项目（QT-2025-029）