目的 基于斑马鱼模型研究黄芩素的抗焦虑作用。方法 将斑马鱼分为对照组、模型组、黄芩素组和地西泮组，除对照组外，其余各组均通过不可预期慢性应激（unpredictable chronic stress，UCS）诱导斑马鱼焦虑模型。给予药物干预后，通过新缸测试检测斑马鱼的行为学变化；采用ELISA测定应激反应生物标志物皮质醇和脑组织神经递质5-羟色胺（5-hydroxytryptamine，5-HT）水平；采用qRT-PCR检测脑组织5-HT合成限速酶色氨酸羟化酶2（tryptophan hydroxylase 2，TPH2）、5-羟色胺1ab受体（5-hydroxytryptamine 1ab receptors，5-HT_1abR）、白细胞介素-1β（interleukin-1β，IL-1β）、核因子-κB（nuclear factor-κB，NF-κB）和肠道IL-1β、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、NF-κB的基因表达；采用Western blotting检测脑组织5-羟色胺1A受体（5-hydroxytryptamine 1A receptors，5-HT_1AR）的蛋白表达；采用16S rRNA微生物多样性测序技术对肠道菌群组成进行检测分析。结果 UCS处理后斑马鱼产生焦虑样行为，肠道菌群物种总数和多样性减少，气单胞菌属Aeromonas比例增加。与模型组比较，黄芩素干预后斑马鱼在水缸底部的停留时间显著减少（P＜0.001），皮质醇水平显著降低（P＜0.001），脑组织5-HT水平显著升高（P＜0.001），脑组织TPH2基因表达显著升高（P＜0.05），脑组织IL-1β、NF-κB和肠道IL-1β、IL-6、TNF-α、NF-κB基因表达显著降低（P＜0.05、0.01、0.001），脑组织5-HT_1AR蛋白表达水平显著降低（P＜0.001），肠道菌群物种丰富度和多样性增加，2 mg/L黄芩素组脑组织5-HT_1abR基因表达显著降低（P＜0.01），1、4 mg/L黄芩素组脑组织5-HT_1abR基因表达显著升高（P＜0.05、0.001）。结论 黄芩素对UCS诱导的斑马鱼焦虑样行为有一定保护作用，其可能是通过抗炎和调节肠道菌群，抑制斑马鱼皮质醇的过量产生，维持5-HT的正常分泌而发挥抗焦虑作用。

Objective To study the anti-anxiety effect of baicalein based on zebrafish model. Methods The zebrafish were divided into control group, model group, baicalein group and diazepam group. Except for the control group, all other groups underwent the induction of a zebrafish anxiety model through unpredictable chronic stress (UCS). After drug intervention, the behavior changes of zebrafish were evaluated through novel tank test. ELISA was used to measure the levels of stress response biomarkers cortisol and brain neurotransmitter serotonin 5-hydroxytryptamine (5-HT). qRT-PCR was employed to detect the gene expressions of tryptophan hydroxylase 2 (TPH2), a rate-limiting enzyme for 5-HT synthesis in brain tissue, 5-hydroxytryptamine 1ab receptors (5-HT_1abR), interleukin-1β (IL-1β), nuclear factor-κB (NF-κB), as well as intestinal IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and NF-κB. Western blotting was used to detect the protein expressions of 5-hydroxytryptamine 1A receptors (5-HT_1AR) in brain tissue. The composition of intestinal microbiota was analyzed using 16S rRNA microbial diversity sequencing technology. Results After UCS treatment, zebrafish exhibited anxiety-like behavior, with a decrease in the total number and diversity of intestinal microbiota species, and an increase in the proportion of Aeromonas. Compared with model group, after intervention with baicalein, the dwell time of zebrafish at the bottom of the tank was significantly reduced (P < 0.001), cortisol level was significantly decreased (P < 0.001), 5-HT level in brain tissue was significantly increased (P < 0.001), gene expression of TPH2 in brain tissue was significantly increased (P < 0.05), gene expressions of IL-1β, NF-κB in brain tissue and IL-1β, IL-6, TNF-α, NF-κB in intestine were significantly decreased (P < 0.05, 0.01, 0.001), the protein expression of 5-HT_1AR in brain tissue was decreased (P < 0.001), species richness and diversity of intestinal microbiota species were increased, the gene expression of 5-HT_1abR in brain tissue was significantly reduced in 2 mg/L baicalein group (P < 0.01), while the gene expression of 5-HT_1abR in brain tissue was significantly increased in 1, 4 mg/L baicalein groups (P < 0.05, 0.001). Conclusion Baicalein has a certain protective effect on UCS-induced anxiety-like behavior in zebrafish, which may be achieved by anti-inflammatory and regulating gut microbiota, inhibiting excessive production of cortisol in zebrafish, maintaining normal secretion of 5-HT, and exerting anti-anxiety effects.

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国家自然科学基金资助项目（22566026）；内蒙古自治区高等学校科学技术研究项目（NJZY23097）；内蒙古自治区自然科学基金资助项目（2023LHMS08076）