基于生物信息学探究鳖甲煎丸对肝细胞癌的调控机制  

Exploring Regulatory Mechanism of Biejiajian Pill(鳖甲煎丸)on Hepatocellular Carcinoma Based on Bioinformatics

作　　者：于欣萍 王诗尧 孟庆刚[1] YU Xinping;WANG Shiyao;MENG Qinggang(Beijing University of Chinese Medicine,Beijing 100102,China)

机构地区：[1]北京中医药大学,北京100102

出　　处：《中华中医药学刊》2025年第4期82-89,I0022-I0026,共13页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82174530)。

摘　　要：目的基于生物信息学探究肝癌发生发展的潜在分子机制,筛选并验证鳖甲煎丸对肝癌起调控作用的机制和靶点。方法下载GEO数据库中的肝细胞癌(hepatocellular carcinoma,HCC)单细胞数据,处理后进行通讯分析、富集与代谢分析、细胞亚群再分析。接下来,收集鳖甲煎丸药物成分及作用靶点,结合转录组学结果,确定鳖甲煎丸与HCC的交集靶点并分析。最后,从PDB数据库和PubChem数据库中获取蛋白和小分子信息,模拟药-靶分子对接;通过计算机构建动力学模拟环境,评估交互作用。收集鳖甲煎丸药物成分及作用靶点,分析其与HCC的交集靶点;从PDB数据库和PubChem数据库中获取蛋白和小分子信息,模拟药-靶分子对接;通过计算机构建动力学模拟环境,评估交互作用。结果转录组学结果显示,HCC癌旁组中细胞间通讯更为活跃;细胞大多富集在细胞周期检查点和免疫反应相关通路;肝细胞代谢活跃,免疫细胞代谢抑制;自然杀伤(natural killer cell,NK)细胞逐渐由具备正常杀伤能力向低杀伤能力演化、肝细胞逐渐由正常肝细胞向癌细胞演化。网络药理学结果显示,鳖甲煎丸调控HCC的潜在作用靶点有124个,大多富集在免疫反应、炎症反应、糖酵解、白介素-17等通路。选择关键蛋白与药物潜在作用靶点进行分子对接,对结合亲和力最强的前三者进行动力学模拟,结果显示这三种受体-配体复合物结合较稳定。结论HCC细胞可能通过扰乱细胞周期和免疫功能促进其恶性增殖和免疫逃逸;鳖甲煎丸可能通过调节抗炎、免疫反应、细胞分裂等通路达到抗肿瘤效果;关键的药-靶关系在分子对接与分子动力学验证中得到了较好结果,证明其具有较好的亲和力。Objective To explore the potential molecular mechanisms underlying the occurrence and development of liver cancer based on bioinformaticsand to screen and validate the mechanisms and targets of Biejiajian Pill(鳖甲煎丸,BJJP)on liver cancer.Methods Single-cell data of hepatocellular carcinoma(HCC)was downloaded from the GEO database,processedand subjected to communication analysis,enrichment and metabolic analysis,and reanalysis of cellular subpopulations.Subsequently,the components and action targets of BJJP were collected,and in conjunction with transcriptomic results,the intersection targets between BJJP and HCC were identified and analyzed.Finally,protein and small molecule information was obtained from the PDB and PubChem databases to simulate drug-target molecular docking.A computational dynamics simulation environment was constructed to assess the interactions.Results Transcriptomic analysis revealed that intercellular communication was more active in the peritumoral group of HCC.The cells were predominantly enriched in pathways related to cell cycle checkpoints and immune responses.The hepatocyte metabolism was active,while immune cell metabolism was suppressed.The natural killer(NK)cells gradually evolved from possessing normal cytotoxic capabilities to lower capabilities,and hepatocytes gradually transformed from normal to cancerous cells.Network pharmacology results showed that BJJP potentially regulated 124 targets in HCC,mostly enriched in pathways such as immune response,inflammatory response,glycolysisand interleukin-17.Molecular docking was performed with key proteins and potential drug action targets,and the top three with the strongest binding affinity were subjected to dynamic simulation,which showed that these three receptor-ligand complexes were relatively stable.Conclusion HCC cells may promote malignant proliferation and immune escape by disrupting cell cycle and immune functions.BJJP may achieve anti-tumor effects by regulating pathways such as anti-inflammatory,immune responseand cell

关 键 词：肝癌 鳖甲煎丸 scRNA-seq分析 分子动力学模拟 分子对接 

分 类 号：R289.5[医药卫生—方剂学]