黄芩苷对慢性不可预知温和应激模型小鼠海马炎症反应的影响及网络药理学分析

The Effect of Baicalin on Hippocampal Inflammatory Response in Chronic Unpredictable Mild Stress Model Mice and Network Pharmacological Analysis

摘要: 目的：整合网络药理学预测与体内动物实验，探究黄芩苷改善慢性不可预知温和应激(CUMS)小鼠抑郁样行为、缓解海马炎症损伤的潜在分子机制。方法：依托多个数据库筛选黄芩苷作用靶点与抑郁症疾病靶点，取交集构建PPI蛋白互作网络，完成GO、KEGG富集分析；建立CUMS抑郁小鼠模型，设置空白、模型、氟西汀、黄芩苷高低剂量组，观测小鼠体重、旷场行为，结合海马HE染色与ELISA检测IL-1β、IL-6、TNF-α炎症因子水平。结果：筛选出IL6、TNF、IL1B、CREB1等核心靶点，富集通路集中于炎症反应、免疫应答、神经信号调控；模型小鼠活动减少、海马神经元受损、炎症因子显著升高，高剂量黄芩苷可显著改善小鼠行为与海马病理损伤，下调炎症因子(P < 0.05)。结论：黄芩苷能够缓解CUMS诱导的抑郁行为与海马神经炎症，其药效机制与调控炎症相关靶点通路密切相关，为黄芩苷干预抑郁症神经炎症机制研究提供实验支撑。

Abstract: Objective: By integrating network pharmacological predictions with in vivo animal experiments, the potential molecular mechanisms by which baicalin improves depression-like behaviors and alleviates hippocampal inflammatory damage in mice with chronic unpredictable mild stress (CUMS) were explored. Method: Relying on multiple databases, the action targets of baicalin and the disease targets of depression were screened. The intersection was taken to construct the PPI protein interaction network, and GO and KEGG enrichment analyses were completed. A CUMS depression mouse model was established. Blank, model, fluoxetine, and baicalin high-dose and low-dose groups were set up. The body weight and open-field behavior of mice were observed. The levels of inflammatory factors IL-1β, IL-6, and TNF-α were detected by hippocampal HE staining and ELISA. Result: Core targets such as IL6, TNF, IL1B, and CREB1 were screened out, and the enrichment pathways were concentrated on inflammatory responses, immune responses, and neural signal regulation. The activity of model mice was reduced, hippocampal neurons were damaged, and inflammatory factors were significantly increased. High-dose baicalin could significantly improve the behavior and hippocampal pathological damage of mice and downregulate inflammatory factors (P < 0.05). Conclusion: Baicalin can alleviate depressive behaviors and hippocampal neuroinflammation induced by CUMS. Its pharmacological mechanism is closely related to the regulation of inflammation-related target pathways, providing experimental support for the study of baicalin’s intervention in the neuroinflammation mechanism of depression.