目的 基于网络药理学、分子对接及动物实验验证揭示复方黄芪汤抗肺癌分子机制。方法 通过网络药 理学预测复方黄芪汤抗肺癌的核心成分、靶基因和关键信号通路并进行分子对接；构建 Lewis 荷瘤小鼠模型， 设立空白对照组、荷瘤对照组、PD-1 抗体组（10 mg·kg-1 ）及复方黄芪汤低、高剂量组（30、60 g·kg-1 ），统计肿 瘤质量和抑瘤率；苏木精-伊红（HE）染色法检测肿瘤及肺组织病理变化，免疫组化法检测肿瘤组织中微血管密 度蛋白（Factor Ⅷ）表达，酶联免疫吸附测定法（ELISA）检测血清中血管内皮生长因子（VEGF）含量，Western Blot 法检测肿瘤组织中磷酸化蛋白激酶 B（p-AKT）和蛋白激酶 B（AKT）蛋白表达。结果 从数据库筛选出复方 黄芪汤活性成分 56 个，交集靶点 181 个，核心靶点 9 个，对应活性成分 8 个；基因本体（GO）分析及基因组百 科全书（KEGG）信号通路富集分析结果显示，其主要通过调控 PI3K-AKT、JAK-STAT、EGFR 酪氨酸激酶抑制 剂耐药等信号通路抗肺癌。分子对接提示黄芪紫檀烷苷与 VEGF 及山柰酚、熊竹素、异鼠李素与蛋白激酶 Bα （AKT1）具有良好结合力。动物实验验证结果显示，与荷瘤对照组比较，复方黄芪汤高剂量组能显著抑制肿瘤 生长，降低肿瘤质量（P＜0.01）。HE 染色结果显示肿瘤细胞的细胞核大且核分裂相明显，而复方黄芪汤干预后 肿瘤细胞排列松散，细胞间隙大，细胞活跃度低。与荷瘤对照组比较，复方黄芪汤高剂量组能显著降低 Factor Ⅷ水平（P＜0.001）及 VEGF 含量（P＜0.01）；Western Blot 结果显示其能显著下调 p-AKT/AKT 比值（P＜0.01）。 结论 复方黄芪汤可能通过干预 VEGF-AKT 信号通路，抑制肿瘤血管生成，进而发挥抑瘤作用。

Objective To elucidate the molecular mechanism of Compound Astragali Radix Decoction （CARD） against lung cancer through network pharmacology， molecular docking， and experimental validation in animals. Methods Network pharmacology was employed to predict the core components， target genes， and key signaling pathways of CARD against lung cancer， followed by molecular docking verification. A Lewis tumor-bearing mouse model was established and divided into blank control，tumor-bearing control，PD-1 antibody （10 mg·kg-1 ），low-dose CARD （30 g·kg-1 ），and high-dose CARD （60 g·kg-1 ） groups. Tumor mass and inhibition rate were measured. Hematoxylin-eosin （HE） staining was used to examine pathological changes in tumor and lung tissues；immunohistochemistry was performed to detect microvessel density （Factor Ⅷ） expression in tumor tissues；enzyme-linked immunosorbent assay （ELISA） was used to measure serum vascular endothelial growth factor （VEGF） levels； and Western Blot was employed to assess phosphorylated protein kinase B （p-AKT） and total AKT protein expression in tumor tissues. Results There were 56 active components and 181 common targets of CARD were identified from databases， with 9 core targets and 8 corresponding active components selected. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses indicated that CARD exerts anti-lung cancer effects primarily by regulating the PI3K-AKT，JAK-STAT，and EGFR tyrosine kinase inhibitor resistance signaling pathways. Molecular docking demonstrated strong binding affinity between astrapterocarpan and VEGF， as well as between kaempferol， jaranol， and isorhamnetin with protein kinase Bα（AKT1）. Animal experiments revealed that， compared with the tumor-bearing control group，the high-dose CARD group significantly inhibited tumor growth and reduced tumor mass （P＜0.01）. HE staining showed that tumor cells in the control group had large nuclei and prominent mitotic figures， whereas CARD intervention resulted in loosely arranged tumor cells with wide intercellular spaces and reduced cell activity. The high-dose CARD group significantly decreased Factor Ⅷ levels （P＜0.001） and VEGF content （P＜ 0.01） compared with the tumor-bearing control group. Western Blot results indicated a significant downregulation of the p-AKT/AKT ratio （P＜0.01）. Conclusion Compound Astragali Radix Decoction may inhibit tumor angiogenesis and exert anti-tumor effects by interfering with the VEGF-AKT signaling pathway.

R285.5

国家自然科学基金项目（82074016，81603296）；江苏省中医药管理局项目（2020ZX18）；常州市卫生健康委员会重大项目（ZD202028）； 常州市科技计划项目（CM20223006，CJ20219008）；2024年江苏省研究生科研与实践创新计划项目（SJCX24_0919）。