目的 探讨健脑补肾丸（W）与健脑补肾口服液（KFY）安神作用药效差异并预测其安神作用机制。方法 通过ip对氯苯丙氨酸（PCPA）构建小鼠失眠模型，给予不同剂量的W（0.225、0.450、0.900 g·kg^-1）与KFY（1.85、3.90、7.80 mL·kg^-1）干预7 d，记录小鼠体质量变化，通过旷场实验评估小鼠自发活动，戊巴比妥钠睡眠实验观察小鼠睡眠潜伏期、睡眠持续时间，苏木精-伊红染色观察海马组织病理变化，酶联免疫吸附试验检测脑内5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）、γ-氨基丁酸（GABA）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）及肿瘤坏死因子-α（TNF-α）的水平，Western blotting检测下丘脑中5-羟色胺1A受体（5-HT1A）与γ-氨基丁酸1A受体（GABRA1）蛋白的表达，探讨其改善失眠样行为、神经炎症及调节睡眠相关神经递质的药效活性并预测其作用机制，运用综合权重法与主成分分析法对上述药效指标进行综合评价，比较W与KFY安神作用的疗效差异。结果 动物实验结果显示，W与KFY可显著促进小鼠体质量增长（P＜0.05、0.01），显著减少旷场实验中小鼠的移动距离、平均速度和跨格次数（P＜0.05、0.001），降低戊巴比妥钠睡眠实验中小鼠睡眠潜伏期，并增加睡眠持续时间（P＜0.05、0.01、0.001），改善小鼠海马神经元病理形态，显著上调全脑中5-HT、GABA水平（P＜0.05、0.01、0.001）以及下丘脑中5-HT1A、GABRA1的表达（P＜0.05、0.01、0.001），并显著下调全脑中NE、DA、IL-6、IL-1β和TNF-α水平（P＜0.05、0.01、0.001）。综合权重法与主成分分析法药效比较结果显示，W及KFY药效均表现出剂量相关性增强的特点，且在相同临床等效剂量下，KFY整体药效更优。结论 W与KFY可通过改善失眠样行为、调节神经递质及抑制神经炎症起到治疗失眠的作用，且KFY综合评分更优。

Objective Explore the differences in the tranquilizing effects between Jiannao Bushen Wan (W) and Jiannao Bushen Oral Liquid (KFY), and predict their mechanisms of action for tranquilization. Methods A mouse model of insomnia was established by intraperitoneal injection of parachlorophenylalanine (PCPA). Different doses (0.225, 0.450, and 0.900 g·kg^-1) of W and KFY were administered for intervention. The spontaneous activity of mice was assessed using the open field test, while sleep latency and sleep duration were observed through the pentobarbital sodium-induced sleep test. Histopathological changes in the hippocampus were examined using hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to detect the levels of 5- hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), γ-aminobutyric acid (GABA), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the brain. Western blotting was used to measure the protein expression of 5- hydroxytryptamine receptor 1A (5-HT1A) and γ-aminobutyric acid A receptor alpha 1 (GABRA1) in the hypothalamus, aiming to investigate their pharmacodynamic activities in improving insomnia-like behaviors, neuroinflammation, and regulating sleep-related neurotransmitters, as well as to predict their mechanisms of action. The comprehensive weight coefficient method and principal component analysis were applied to comprehensively evaluate the aforementioned pharmacodynamic indicators, comparing the differences in the tranquilizing effects between W and KFY. Results The results of the animal experiment showed that both W and KFY significantly reduced the movement distance, average speed, and grid-crossing count of mice in the open field test (P<0.05 and 0.01), decreased the sleep latency and increased the sleep duration in the pentobarbital sodium-induced sleep test (P<0.05 and 0.01). Furthermore, they ameliorated the pathological morphology of hippocampal neurons, significantly upregulated the levels of 5-HT and GABA in the whole brain (P<0.05, 0.01 and 0.001) and the expression of 5-HT1A and GABRA1 in the hypothalamus (P<0.05, 0.01 and 0.001), and significantly downregulated the levels of NE, DA, IL-6, IL-1β, and TNF-α in the whole brain (P<0.05, 0.01 and 0.001). The pharmacodynamic comparison results using the Comprehensive Weight Coefficient Method and Principal Component Analysis indicated that the efficacy of both W and KFY exhibited a dose-dependent enhancement. Moreover, at the same clinically equivalent dose, KFY demonstrated superior overall pharmacodynamic efficacy. Conclusion W and KFY can exert therapeutic effects on insomnia by ameliorating insomnia-like behaviors, regulating neurotransmitters, and inhibiting neuroinflammation, with KFY demonstrating superior efficacy.

R965

山东省重点研发计划（2025CXPT123）