目的 借助生物信息学与网络药理学探究华蟾素缓解奥沙利铂诱导的周围神经毒性的靶点及作用机制。方法 通过SwissTarget Prediction、PharmMapper、SuperPred数据库预测华蟾素靶点，从GeneCards、OMIM、Harmonizome 3.0数据库获取奥沙利铂诱导的周围神经毒性靶点，结合GEO数据库奥沙利铂处理后的差异基因，经交集分析得到共同靶点。运用DAVID数据库进行基因本体（gene ontology，GO）功能和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析，通过PPI网络及机器学习筛选核心靶点，采用AutoDock、Gromacs进行分子对接与动力学模拟，PyMOL、QtGrace 2.6和Python 3.7辅助可视化，利用单细胞分析探究核心靶点的特异性表达景观。结果 筛选华蟾素活性成分37种（如嚏根草醇、远华蟾毒精等），获得共同靶点45个；PPI及机器学习共同确定血小板衍生生长因子受体β（platelet-derived growth factor receptor beta，PDGFRB）、细胞周期蛋白D1（Cyclin D1，CCND1）等核心靶点。分子对接显示远华蟾毒精等与CCND1、PDGFRB结合能＜-5 kcal/mol，动力学模拟证实PDGFRB与远华蟾毒精结合稳定，单细胞分析提示华蟾素靶向基质细胞PDGFRB重塑神经支持性微环境。结论 华蟾素在急性奥沙利铂所致周围神经病变阶段通过靶向PDGFRB阳性神经基质细胞，激活磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）-蛋白激酶B（protein kinase B，Akt）信号通路发挥神经保护作用，为化疗神经毒性早期预防提供理论依据。

Objective To investigate the targets and mechanisms of Huachansu in alleviating oxaliplatin-induced peripheral neurotoxicity using bioinformatics and network pharmacology. Methods The targets of Huachansu were predicted via SwissTarget Prediction, PharmMapper, and SuperPred databases. Targets associated with oxaliplatin-induced peripheral neurotoxicity were retrieved from GeneCards, OMIM, and Harmonizome 3.0 databases. Combined with differential genes after oxaliplatin treatment from the GEO database, common targets were obtained through intersection analysis. The DAVID database was used for gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Core targets were screened via the PPI network and machine learning. Single-cell analysis was performed to explore the specific expression landscape of the core targets. AutoDock and Gromacs were employed for molecular docking and molecular dynamics simulation, with visualization assisted by PyMOL, QtGrace 2.6 and Python 3.7. Results A total of 37 active components of Huachansu were identified (e.g., telocinobufagin, hellebrigenol). Forty-five common targets were obtained. CCND1, PDGFRB, and other core targets were jointly determined by PPI network and machine learning. Molecular docking showed that telocinobufagin and other components exhibited binding energies of < -5 kcal/mol with Cyclin D1 (CCND1) and platelet-derived growth factor receptor beta (PDGFRB). Molecular dynamics simulation confirmed the stable binding between PDGFRB and telocinobufagin. Single-cell analysis suggested that Huachansu targets PDGFRB in stromal cells to reshape the neuro-supportive microenvironment. Conclusion Huachansu exerts neuroprotective effects at the acute OIPN stage by targeting PDGFRB⁺ neural stromal cells and activating the phosphatidylinositol-3-hydroxykinase (PI3K)-protein kinase B (Akt) signaling pathway, providing a theoretical basis for the early prevention of chemotherapy-induced neurotoxicity.

Q811.4;R285

湖北省自然科学基金资助项目（2024AFB290）；肿瘤微环境与免疫治疗湖北省重点实验室（三峡大学）开放基金资助项目（2024ZLGY06，2025ZLKF08）