目的 旨在基于网络药理学筛选绞股蓝皂苷XVII改善脑出血后神经损伤的潜在靶点与通路，并通过体内外实验验证其作用及对磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B1（Akt）信号通路的调控机制。方法 通过网络药理学平台筛选绞股蓝皂苷XVII与脑出血的交集靶点，构建蛋白质相互作用网络（PPI）并进行关键通路的富集分析；通过分子对接验证靶点结合能，利用细胞实验、动物实验探索绞股蓝皂苷XVII治疗脑出血的分子机制。通过氯化血红素诱导SH-SY5Y细胞模拟脑出血模型后，使用CCK-8测细胞活性、荧光探针检测细胞内活性氧（ROS）水平；实时荧光定量聚合酶链式反应（RT-qPCR）检测肿瘤坏死因子（TNF）、白细胞介素（IL）-1β、胰岛素样生长因子1（IGF1）、表皮生长因子受体（EGFR）、磷酸肌醇3激酶调控亚基1（PIK3R1）的mRNA表达水平。将60只SD大鼠随机分成假手术组、模型组、绞股蓝皂苷XVII（20、40 mg/kg）组，采用自体血注射法构建大鼠脑出血模型，评估大鼠神经功能评分，干/湿质量法检测脑组织含水量，HE染色及尼氏检测血肿周围脑组织病理变化，试剂盒检测氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）及炎症因子TNF-α、IL-1β水平，Western blotting检测p-PI3K、PI3K、p-Akt、Akt蛋白表达水平。结果 网络药理学筛选出166个共同靶点，PPI分析揭示核心靶点（PIK3R1、Akt1等），KEGG富集提示PI3K/Akt为核心通路。体外实验表明，绞股蓝皂苷XVII显著提高细胞存活率、抑制ROS生成，并下调TNF、IL-1β、IGF1、EGFR、PIK3R1 mRNA表达。体内实验证实，绞股蓝皂苷XVII能够降低大鼠神经功能评分、减少脑水肿，改善血肿周围脑组织病理损伤，提高SOD活性、降低MDA水平及炎症因子TNF-α、IL-1β水平，显著上调PI3K、Akt的磷酸化水平（P＜0.05、0.01、0.001）。结论 绞股蓝皂苷XVII可能通过调控PI3K/Akt通路改善脑出血神经损伤。

Objective To screen potential targets and pathways of gypenoside XVII in ameliorating neurological impairment following intracerebral hemorrhage through network pharmacology approaches, and further validate its therapeutic effects along with the regulatory mechanisms on the PI3K/Akt signaling pathway via both in vitro and in vivo experiments. Methods Network pharmacology platforms were used to screen common targets of gypenoside XVII and intracerebral hemorrhage, followed by PPI network construction and pathway enrichment analysis. Molecular docking was performed to validate target binding activity, while cellular and animal experiments were conducted to explore the molecular mechanism of gypenoside XVII in intracerebral hemorrhage treatment. Hemin-induced SH-SY5Y cell model mimicking intracerebral hemorrhage was established, and cell viability was assessed using the CCK-8 assay. Intracellular reactive oxygen species (ROS) levels were measured via fluorescent probes. RT-qPCR was used to detect mRNA expression levels of TNF, IL-1β, IGF1, EGFR, and PIK3R1. Sixty Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group, and gypenoside XVII (20, 40 mg/kg) group. Intracerebral hemorrhage model was constructed using autologous blood injection. Neurological function scores, cerebral edema (dry-wet weight method), histopathological changes in perihematomal brain tissue (HE and Nissl staining), oxidative stress markers (SOD, MDA), inflammatory cytokines (TNF-α, IL-1β), and protein expression levels of p-PI3K, PI3K, p-Akt, and Akt were evaluated. Results Network pharmacology identified 166 common targets, with PPI analysis revealing core targets (PIK3R1, Akt1), and KEGG enrichment highlighting the PI3K/Akt pathway as central. In vitro, gypenoside XVII significantly increased cell viability, inhibited ROS generation, and downregulated TNF, IL-1β, IGF1, EGFR, PIK3R1 mRNA expression. In vivo, gypenoside XVII reduced neurological deficits, decreased cerebral edema, alleviated perihematomal pathological damage, enhanced SOD activity, lowered MDA and inflammatory cytokine levels (TNF-α, IL-1β), and upregulated phosphorylation levels of PI3K and Akt (P < 0.05, 0.01, 0.001). Conclusion Gypenoside XVII may improve neurological injury after intracerebral hemorrhage by modulating the PI3K/Akt pathway.

R286.1

江苏省卫生健康委科研项目（K2023044）；盐城市科技项目基础研究计划（YCBK2024072）