【目的】 运用网络药理学方法及临床试验验证，探讨参乌益智胶囊治疗卒中后认知障碍（PSCI）的作用机制。【方法】 前 瞻性纳入2022年8月~2024年2月安徽中医药大学附属太和中医院收治的90例PSCI患者，采用随机数字表法将患者随机分为 对照组和试验组，每组各45例。对照组予以PSCI常规治疗，试验组在对照组的基础上加用参乌益智胶囊治疗，疗程为28 d。 观察 2 组患者治疗前后简易精神状态检查量表（MMSE）评分、蒙特利尔认知评估量表（MoCA）评分及血清肿瘤坏死因子 α （TNF-α）、白细胞介素 6（IL-6）等炎症因子的变化情况，并记录 2 组患者不良事件发生情况，评价 2 组治疗方案的安全性。 基于网络药理学方法，运用 TCMSP及查阅文献获得参乌益智胶囊有效活性成分，运用 GeneCards等数据库得到 PSCI疾病靶 点，将共同靶点输入至 STRING 数据库构建 PPI 网络，通过 Cytoscape 3.9.0 构建参乌益智胶囊-PSCI-靶点网络图，运用 DAVID进行GO及KEGG通路富集分析，再通过分子对接验证结合活性。【结果】（1）临床研究方面，治疗28 d后，2组患者的 MMSE、MoCA评分均较治疗前升高（P < 0.05），且试验组的升高幅度均明显优于对照组（P < 0.05）；血清TNF-α、IL-6水平 均较治疗前降低（P < 0.05），且试验组的降低幅度均明显优于对照组（P < 0.05）；同时，2组患者在试验过程中均未见明显不 良反应，具有较高的安全性。（2）网络药理学方面，参乌益智胶囊活性成分共92个，靶点803个，疾病靶点5 209个，交集靶 点556个，核心靶点为AKT1、TNF、IL-6、TP53、IL-1B，关键化合物为脱氧三尖杉酯碱、洋川芎醌、芫花素等，富集得到 1 812个 GO 条目，其中细胞成分（CC）154个，生物学过程（BP）1 332个，分子功能（MF）326个，富集到 195条 KEGG 信号通 路；分子对接结果显示，参乌益智胶囊关键化合物与核心靶点间具有良好的结合活性。【结论】 参乌益智胶囊治疗PSCI临床 疗效显著，多成分可能通过AKT1、TNF、IL-6等靶点作用于信号通路而发挥治疗PSCI的作用。

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of poststroke cognitive impairment（PSCI）by using network pharmacology methods and clinical trial validation. Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024. The patients were randomly divided into the control group and the trial group by random number table method，with 45 cases in each group. The control group was treated with conventional treatment for PSCI，and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group. The treatment course for the two groups covered 28 days. The changes of Mini-Mental State Examination（MMSE）score，Montreal Cognitive Assessment （MoCA）score， and the serum levels of inflammatory factors such as tumor necrosis factor α（TNF - α）and interleukin 6（IL-6）in the patients of the two groups were observed before and after treatment. Moreover，the incidences of adverse events in the two groups were recorded，thus to evaluate the safety of the treatment regimens in the two groups. And then the network pharmacological research was performed. TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule，GeneCards and other databases were used to obtain the PSCI disease targets，and the common targets were inputted into the STRING database to construct the PPI network. Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets， DAVID was used to perform GO and KEGG pathway enrichment analysis，and then molecular docking was used to verify the binding activity. Results（1）The results of clinical trial showed that after 28 days of treatment，the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment（P < 0.05）， and the increase of the scores in the trial group was significantly superior to that in the control group（P < 0.05）. The serum levels of TNF-α and IL-6 were decreased compared with those before treatment（P < 0.05），and the decrease in the trial group was significantly superior to that in the control group（P < 0.05）. During the trial，both groups of patients did not show obvious adverse reactions， with high safety.（2）The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients， 803 targets， 5 209 disease targets and 556 intersection targets. The core targets were AKT1，TNF，IL-6，TP53 and IL-1B，and the key compounds were deoxyharringtonine，senkyunone and genkwanin. The GO enrichment analysis obtained 1 812 GO entries，of which 154 entries were related with cellular component（CC），1 332 entries were related with biological process （BP），and 326 entries were related with molecular function（MF）. The KEGG pathway enrichment analysis yielded 195 signaling pathways. The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets. Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable， and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1，TNF，and IL-6. The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.

R277.7

安徽省中医药管理局科研项目（编号：2022CCYB16）；安徽省高等学校科学研究项目（编号：2022AH050476）；安徽中医药大学 临床科研项目（编号：2023LCTH01）