基于代谢网络调控融合生物信息学的人参煎用于2型糖尿病胰岛素抵抗物质基础及作用机制研究

Based on the holistic theory of traditional Chinese medicine（TCM）and proposed on the basis of preliminary study，the classical decoction of Ginseng and Radix Puerariae with curative effect of the treatment of diabetic is the research object，with integration of interdisciplinary technology, such as chemometrics, metabolomics, network pharmacology and bioinformatics, and development of relations of characterization spectrum between effect components in vivo in Serum Pharmaceutical Chemistry and global efficacy in metabonomics for clarifying effective substance of decoction of Ginseng and Radix Puerariae to treat type 2 diabetic by Suport Vector Machine (SVM).In addition, using network Pharmacology to construct network of effect components (Groups) and protein targets, the above results verified Pharmacophore targets (Groups) by molecular biological technology, constructed its molecular regulatory networks and signaling pathways to improve insulin resistance in type 2 diabetes, revealed deeply mechanism of action of decoction of Ginseng and Radix Puerariae to treat type 2 diabetes and explained scientific connotation of Synergistic effect of multi components and multi targets in TCM, which provide scientific basis for clinical application and further development of decoction of Ginseng and Radix Puerariae. Above all, the study explore the constructions of interlamination progressive research model of “corrections of spectrogram and pesticide effect - targets’ prediction by Network pharmacology elucidation of mechanism by Molecular biology”, improve efficiency to study pharmacodynamic substance and mechanism of Chinese herbal compound prescription, and provide reference for the research of traditional Chinese medicine compound prescription .

本课题依据中医整体观理论，拟在前期研究基础上，以疗效确切的治疗糖尿病经典方剂人参煎为研究对象，整合化学计量学、方证代谢组学、网络药理学及生物信息学等多学科交叉技术，采用SVM开展人参煎LC-MS的血清药物化学体内效应成分表征谱与代谢组学整体药效表征谱的关联研究，明确人参煎多途径治疗糖尿病的药效物质；利用网络药理学方法构建效应成分（群）—蛋白靶点作用网络，基于以上结果采用分子生物学技术验证药效成分（群）作用靶点，构建人参煎改善2型糖尿病胰岛素抵抗的分子调控网络和信号通路，深入揭示人参煎治疗糖尿病的作用机制，阐释中药多成分多靶点协同作用的科学内涵，为该方剂的临床应用和深入开发提供科学依据。并探索构建“谱效关联发现药效物质—网络药理学预测作用靶点-分子生物学阐明药效机制”层间递进研究模式，提高中药复方药效物质及作用机制研究效率，为中药复方研究提供借鉴。

本研究基于代谢网络调控融合生物信息学的研究策略，以人参煎为研究对象，整合化学计量学、方证代谢组学、网络药理学及生物信息学等多学科交叉技术，采用SVM开展人参煎LC-MS的血清药物化学体内效应成分表征谱与代谢组学整体药效表征谱的关联研究，结合PK-PD相关性研究，明确人参煎多途径治疗糖尿病的药效物质；利用网络药理学方法构建效应成分（群）—蛋白靶点作用网络，基于以上结果采用分子生物学技术验证药效成分（群）作用靶点，整合代谢组学和肠道微生物组学研究结果，构建人参煎改善2型糖尿病胰岛素抵抗的分子调控网络和信号通路，深入揭示人参煎治疗糖尿病的作用机制，并探索构建“谱效关联发现药效物质—网络药理学预测作用靶点-分子生物学阐明药效机制”层间递进研究模式。经过四年的研究，基本实现项目申报时的预期研究目标。