目的 通过网络药理学、分子对接技术及分子动力学模拟挖掘火把花根片的分子机制。方法 利用Tripterygium wilfordii Database、ETCM2.0、TCMSP数据库筛选火把花根片的潜在活性成分及其对应靶点。从GeneCards、Drugbank、TTD、DiGSeE数据库数据库获取系膜增殖性肾炎靶点，并通过STRING平台构建蛋白相互作用（PPI）网络。将筛选得到的交集蛋白靶标基因提交至DAVID平台进行基因本体论（GO）功能与京都基因组百科全书（KEGG）通路富集分析。分子对接实验采用AutoDock Tools 1.5.6进行分子对接，并利用PyMoL 2.4.0实现三维可视化呈现。采用GROMACS 2022.6软件包进行分子动力学模拟，分析信号转导和转录活化因子3（STAT3）与雷公藤红素小分子复合物的构象变化机制。结果 共收集到主要活性成分11个及相关靶点蛋白102个，筛选出活性成分相关靶点与疾病靶点交集共67个，核心靶点包括信号转导和转录活化因子3（STAT3）、转录因子（JUN）、GTP焦磷酸激酶（RELA）、组蛋白乙酰转移酶p300抑制剂（EP300）、糖皮质激素受体基因（NR3C1）、雌激素受体1（ESR1）、雄激素受体（AR）。通过富集分析揭示了火把花根片治疗系膜增殖性肾炎可能与对激素的反应、细胞凋亡、细胞因子调节、对氧的反应等生物过程有关，并通过癌症通路、糖尿病并发症晚期糖基化产物（AGE）-晚期糖基化终末产物受体（RAGE）、白细胞介素-17等多条信号通路共同发挥作用。分子对接结果显示，关键活性成分与关键靶点结合性良好。分子动力学模拟结果表明雷公藤红素与STAT3的蛋白质构象更趋于稳定。结论 火把花根片是通过多成分、多靶点、多通路的方式发挥治疗系膜增殖性肾炎的作用，而雷公藤红素与STAT3的蛋白质构象稳定性突出，可能在治疗中起到关键作用，为该制剂在系膜增殖性肾炎的深入研究和临床应用提供理论依据。

Objective To explore the molecular mechanism of the Huobahuagen Tablets through network pharmacology, molecular docking technology and molecular dynamics simulation. Methods Potential active components and corresponding targets of Huobahuagen Tablets were screened by using the Tripterygium wilfordii Database, ETCM2.0, and TCMSP databases. The targets of mesangial proliferative glomerulonephritis were obtained from GeneCards, Drugbank, TTD, and DiGSeE databases, and the PPI network was constructed through the STRING platform. The intersected protein target genes obtained through screening were submitted to the DAVID platform for GO and KEGG pathway enrichment analysis. The molecular docking experiment was conducted using AutoDock Tools 1.5.6 for molecular docking, and PyMoL 2.4.0 was utilized to achieve three-dimensional visualization presentation. Molecular dynamics simulation was performed using the GROMACS 2022.6 software package to analyze the conformational change mechanism of the STAT3 and celastrol. Results A total of 11 main active components and 102 related target proteins were collected. 67 intersections of the target points related to the active components and the disease target points were identified. The core target points include STAT3, JUN, RELA, EP300, NR3C1, ESR1, and AR. Through enrichment analysis, it was revealed that the Huobahuagen Tablets may be involved in treatment of mesangial proliferative glomerulonephritis through various biological processes such as the response to hormones, cell apoptosis, cytokine regulation, and response to oxygen. It also functions through multiple signaling pathways such as cancer pathways, AGE-RAGE pathways, and IL-17 pathways. The molecular docking results showed that the key active components had good binding affinity with the key targets. The molecular dynamics simulation results indicated that celastrol had a more stable protein conformation with STAT3. Conclusion Huobahuagen Tablets exerts its therapeutic effect on mesangial proliferative glomerulonephritis through a multi-component, multi-target, and multi-pathway mechanism. Celastrol have outstanding protein conformational stability with STAT3, which may play a crucial role in treatment and provide a theoretical basis for the in-depth research and clinical application of this formulation in mesangial proliferative glomerulonephritis.

R287.3

重庆市科技部“科技助力经济2020”重点专项（SQ2020YFF0417688）；重庆市技术创新与应用发展专项（CSTB2025TIAD-qykjggX0253）