基于真实世界与靶点网络聚类的茵栀黄颗粒治疗黄疸的联合用药方案及分子机制分析

Combination medication regimen and molecular mechanism analysis of Yinzhihuang Granule in treatment of jaundice based on real world and target network clustering

目的 挖掘茵栀黄颗粒治疗黄疸的核心联用药物方案的临床应用规律,为探索临床不同诊疗思路、用药经验和提高中医药临床证据的循证等级提供参考。方法 基于全国39家医院信息管理系统(hospital information system,HIS)黄疸患者的用药数据,运用Tabu搜索算法,对真实世界茵栀黄颗粒治疗黄疸的联合用药情况进行回顾性分析。同时,采用靶点网络分析核心联合用药方案的分子网络机制,并通过分子对接技术对其作用机制进行验证。结果 根据Tabu搜索算法聚类分析的结果,结合肝病相关指南和文献,识别出3种茵栀黄颗粒治疗黄疸的核心联用药物方案:(1)针对药物性肝损伤导致的黄疸,可以联用谷胱甘肽;(2)针对胆汁淤积导致的黄疸,可以联用亮菌甲素;(3)针对病毒性肝炎导致的黄疸,可以联用双环醇。3种方案的分子网络机制均具有多成分、多靶点、多通路的特点,茵栀黄联用谷胱甘肽治疗黄疸的分子网络机制主要与机体的炎症免疫、Toll样受体信号通路传导、谷胱甘肽代谢通路和细胞死亡负调控的生物过程有关;茵栀黄联用亮菌甲素治疗黄疸的分子网络机制主要与动脉粥样硬化、胆汁分泌等关键通路有关;茵栀黄联用双环醇治疗黄疸的分子网络机制主要与上皮细胞信号转导通路和癌症相关的信号通路有关。结论 数据挖掘得出的茵栀黄颗粒核心联合用药方案,基本符合相关指南及诊疗规范,并对其作用机制进行了探索,为优化临床联合用药、合理用药提供了一定的指导和参考。建议临床实际应用过程中,根据黄疸的疾病进展情况,合理评估临床联合用药方案的疗效及安全性,注意用药配伍禁忌。

Objective To mine the clinical application rules of Yinzhihuang Granule(茵栀黄颗粒)combined with drug regimen in the treatment of jaundice,so as to provide reference for exploring different clinical diagnosis and treatment ideas,medication experience and improving the evidence-based level of clinical evidence of traditional Chinese medicine.Methods Based on the medication data of jaundice patients from 39 hospital information system(HIS)in China,the Tabu search algorithm was used to retrospectively analyze the combination medication of Yinzhihuang Granule in the treatment of jaundice in the real world.At the same time,the molecular network mechanism of the core drug combination regimen was analyzed by the target network,and the mechanism was verified by molecular docking technology.Results According to the results of Tabu search algorithm cluster analysis,combined with liver disease related guidelines and literature,three core combined drug schemes for Yinzhihuang Granule in the treatment of jaundice were identified:(1)For jaundice caused by drug-induced liver injury,glutathione could be combined;(2)For jaundice caused by cholestasis,armillarisin A could be combined;(3)For jaundice caused by viral hepatitis,bicyclol could be combined.The molecular network mechanism of the three regimentsall had the characteristics of multi-component,multi-target and multi-pathway.The molecular network mechanism of Yinzhihuang Granule combined with glutathione in the treatment of jaundice was mainly related to the body’s inflammation and immunity,Toll-like receptor signaling pathway,glutathione metabolism pathway and the biological process of negative regulation of cell death.The molecular network mechanism of Yinzhihuang Granule combined with armillarisin A in the treatment of jaundice was mainly related to key pathways such as atherosclerosis and bile secretion.The molecular network mechanism of Yinzhihuang Granule combined with bicyclol in the treatment of jaundice was mainly related to epithelial cell signal transduction pathway and cancer related signal pathway.Conclusion The core drug combination regimen of Yinzhihuang Granule in this study basically conforms to the relevant guidelines and diagnosis and treatment norms,and its mechanism was explored,which provides certain guidance and reference for optimizing clinical drug combination and rational drug use.It is suggested that the efficacy and safety of clinical combined drug regimen should be reasonably evaluated according to the disease progression of jaundice in clinical practice,and the contraindications of medication compatibility should be paid attention.