目的 基于网络药理学和实验验证，探讨化痰活血解毒方治疗动脉粥样硬化潜在的作用机制。方法 网 络药理学部分：通过 TCMSP 数据库、文献数据库及 DisGeNET 数据库，预测并筛选化痰活血解毒方的有效成 分、相关靶点及动脉粥样硬化的相关靶点；利用 Venny2.1.0 平台获取化痰活血解毒方治疗动脉粥样硬化的核 心靶点，并基于 Metascape 数据库进行 GO 和 KEGG 富集分析，利用 STRING 数据库构建蛋白质相互作用网络， 利用 Cytoscape 3.8.2 软件构建“药物-有效成分-核心靶点”和“信号通路-核心靶点-有效成分”网络；并根据 分析结果，进行分子对接验证。动物实验部分：选取 20 只 ApoE-/-小鼠，随机分为模型组和化痰活血解毒方 组，每组 10 只。模型组及化痰活血解毒方组均给予 16 周高脂饲料喂养，从第 9 周起化痰活血解毒方组连续灌 胃化痰活血解毒方 8 周，模型组予生理盐水灌胃 8 周。正常组选取 10 只 C57BL/6J 小鼠，普通饲料喂养 16 周， 从第 9 周起予生理盐水灌胃。各组灌胃结束后取材，大体油红 O 染色观察主动脉脂质沉积情况；HE 染色观察 颈动脉斑块面积；ELISA 法检测各组血清中 TNF-α、IL-6、IL-1β 及 AGEs 的水平；Western Blot 法检测颈动 脉中 p-P65/P65、RAGE 的蛋白表达水平。结果 网络药理学部分：通过筛选发现化痰活血解毒方共有 79 个有 效成分、1 486 个相关靶点，动脉粥样硬化有 239 个相关靶点；取交集得到核心靶点 70 个，GO 与 KEGG 富集 分析发现 45 个细胞组分、1 376 个生物学过程、88 个分子功能，239 个 KEGG 信号通路；通过分子对接验证发 现，15 组“关键成分-关键靶点”的结合能均小于 0 kcal·mol-1 ，说明关键成分与关键靶点间有很好的亲和力。动 物实验验证部分：化痰活血解毒方可减少小鼠颈动脉斑块面积，降低主动脉脂质沉积，降低血清中 TNF-α、 IL-6、IL-1β 及 AGEs 水平（P＜0.01，P＜0.001，P＜0.000 1），抑制 p-P65/P65、RAGE 的蛋白表达（P＜0.05， P＜0.000 1），从而发挥抗动脉粥样硬化的作用。结论 化痰活血解毒方可通过多成分、多靶点共同参与的形 式，抑制 AGE-RAGE/NF-κB 信号通路，从而调控炎症反应，发挥抗动脉粥样硬化的作用。

Objective To investigate the potential mechanism of the Huatan Huoxue Jiedu Formula in treating atherosclerosis， integrating network pharmacology prediction with experimental validation. Methods Network pharmacology： Active compounds of the formula， their related targets， and atherosclerosis-associated targets were predicted and screened using the TCMSP database，literature databases，and the DisGeNET database. The Venny 2.1.0 platform was utilized to identify core targets of the formula against atherosclerosis. GO and KEGG enrichment analyses were performed using the Metascape database. A protein-protein interaction network was constructed using the STRING database.“Drug-active ingredient-core target” and “signaling pathway-core target-active ingredient” networks were built using Cytoscape 3.8.2 software. Based on the analytical results， molecular docking validation was conducted. Animal experiment： Twenty ApoE-/- mice were randomly divided into a model group and a Huatan Huoxue Jiedu Formula group （n=10 per group）. Both groups were fed a high-fat diet for 16 weeks. From the ninth week onwards，the formula group received the Huatan Huoxue Jiedu Formula by gavage for 8 weeks，while the model group received normal saline by gavage for 8 weeks. Ten C57BL/6J mice were selected as the normal group，fed a standard diet for 16 weeks， and received normal saline by gavage from the ninth week onwards. After the gavage period，all mice were euthanized for sample collection. En face Oil Red O staining was used to assess aortic lipid deposition. Hematoxylin and eosin staining was employed to measure carotid plaque area. Serum levels of TNF- α， IL-6， IL-1β， and AGEs were detected by ELISA. The protein expression levels of p-P65/P65 and RAGE in the carotid artery were determined by Western Blot. Results Network pharmacology screening identified 79 active compounds in the Huatan Huoxue Jiedu Formula， corresponding to 1 486 related targets. A total of 239 atherosclerosis-related targets were identified. The intersection yielded 70 core targets. GO and KEGG enrichment analyses revealed 45 cellular components，1 376 biological processes，88 molecular functions，and 239 KEGG signaling pathways. Molecular docking validation demonstrated that the binding energies of all 15“key component-key target” pairs were less than 0 kcal·mol-1 ，indicating strong affinity between the key components and their targets. Experimental validation showed that the Huatan Huoxue Jiedu Formula reduced carotid plaque area，decreased aortic lipid deposition，lowered serum levels of TNF-α，IL-6，IL-1β，and AGEs，and inhibited the protein expression of p-P65/P65 and RAGE，thereby exerting an anti-atherosclerotic effect. Conclusion The Huatan Huoxue Jiedu Formula exerts its anti-atherosclerotic effect by modulating inflammatory responses through the inhibition of the AGE-RAGE/NF- κB signaling pathway，involving a synergistic mechanism of multiple components and multiple targets.

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国家自然科学基金面上项目（81473507）；河南省自然科学基金青年科学基金项目（232300420273）；河南省科技攻关项目（242102310087， 252102310027，212102311083）；河南省医学科技攻关计划联合共建项目（LHGJ20230690）；河南省中医药科学研究专项课题（2024ZY3030）； 河南省大学生创新创业训练计划项目（S202110471024）。