目的 评价交泰丸和选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors，SSRIs）治疗抑郁症患者的临床疗效，并探讨其作用机制。方法 基于前期的多中心、随机、阳性药平行对照临床试验生物样本数据，将纳入的83例抑郁症患者被分为交泰丸组（n＝25）、交泰丸联合SSRIs组（n＝29）和SSRIs组（n＝29）。采用混合线性模型分析各组治疗前后短链脂肪酸（short-chain fatty acids，SCFAs）、神经炎症标志物［环氧合酶-2（cyclooxygenase-2，COX-2）、前列腺素E₂（prostaglandin E₂，PGE₂）］及脑源性神经营养因子（brain derived neurotrophic factor，BDNF）的变化；通过Spearman相关性与结构方程模型探索治疗后生物标志物与临床症状［汉密尔顿抑郁量表（Hamilton depression rating scale，HAMD）评分］的关联及中介路径。结果 3组患者HAMD评分均较基线显著下降（P＜0.001），但组间无统计学差异。交泰丸组表现出丁酸水平的显著升高（P＝0.002）并维持较高乙酸、丙酸水平；SSRIs组异戊酸、异丁酸、己酸水平升高；交泰丸联合SSRIs组治疗后异丁酸、异戊酸和异己酸水平均显著提升，乙酸水平显著下降；交泰丸联合SSRIs组治疗后BDNF水平显著高于其他两组（P＜0.05）。相关性分析显示，治疗后交泰丸联合SSRIs组的PGE₂与BDNF呈强正相关（r＝0.609，P＜0.001），SSRIs组的COX-2与HAMD评分呈正相关（r＝0.451，P＝0.014），交泰丸组的异己酸与BDNF呈正相关（r＝0.445，P＝0.026）。中介分析提示，在交泰丸联合SSRIs组中，PGE₂通过BDNF影响HAMD评分的间接效应＝−0.065，P＝0.093。结论 交泰丸、SSRIs单独治疗及交泰丸联合SSRIs治疗均能有效缓解抑郁症状，但在调节肠道SCFAs谱、神经炎症及神经营养因子方面表现出不同的作用模式。交泰丸联合SSRIs治疗可能通过调节支链脂肪酸代谢，并促进PGE₂与BDNF之间的正向关联，形成了潜在的有别于单一疗法的作用路径。这些发现为理解不同抗抑郁策略的差异化机制提供了初步证据，提示个性化治疗需考虑患者特定的生物学特征。

Objective To investigate clinical efficacy of Jiaotai Wan (JTW, 交泰丸), and selective serotonin reuptake inhibitors (SSRIs) in patients with depression, and to explore their underlying mechanisms. Methods Based on biological sample data from a previous multicenter, randomized, active-controlled parallel clinical trial, a total of 83 depression patients were divided into three groups: JTW group (n = 25), JTW combined with SSRIs group (n = 29), and SSRIs alone group (n = 29). A mixed linear model was used to analyze changes in short-chain fatty acids (SCFAs), neuroinflammatory markers [cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂)] and brain-derived neurotrophic factor (BDNF) before and after treatment in each group. Spearman correlation and structural equation modeling were used to explore the relationships between post-treatment biomarkers and clinical symptoms [Hamilton depression rating scale (HAMD) scores], and potential mediating pathways. Results HAMD scores decreased significantly from baseline in all three groups (P < 0.001), but there was no significant differences between the groups. The JTW group showed a significant increase in butyrate levels (P = 0.002) and maintained higher levels of acetate and propionate. The SSRIs group was associated with increased levels of isovalerate, isobutyrate, and hexanoate. After treatment, the JTW + SSRIs group showed significant increases in isobutyrate, isovalerate, and isohexanoate levels, and a significant decrease in acetate levels. The combined group had significantly higher BDNF levels than the other two groups (P < 0.05). The PGE₂ levels in the combined group were also higher than in the JTW group both at baseline and after treatment (P < 0.05). Correlation analysis showed a strong positive correlation between PGE₂ and BDNF in the combined group after treatment (r = 0.609, P < 0.001). In the SSRIs group, COX-2 was positively correlated with HAMD score (r = 0.451, P = 0.014). In the JTW group, isohexanoate was positively correlated with BDNF (r = 0.445, P = 0.026). Mediation analysis suggested a potential indirect effect in the combined group, where PGE₂ influenced HAMD scores through BDNF (indirect effect = −0.065, P = 0.093). Conclusion JTW alone, SSRIs alone and JTW combined with SSRIs all can effectively alleviate depressive symptoms. However, they showed different patterns in regulating gut SCFAs, neuroinflammation, and neurotrophic factors. JTW combined with SSRIs may modulate branched-chain fatty acid metabolism and promote a positive association between PGE₂ and BDNF, thereby creating a distinct pathway that differs from single therapies. These findings provide preliminary evidence for understanding the differential mechanisms of various antidepressant strategies, suggesting that personalized treatment should consider patients’ specific biological characteristics.

R285.64

国家自然科学基金面上项目（82074220）