基于代谢组学研究复方血栓通防治糖尿病视网膜病变的组方规律

糖尿病视网膜病变（DR）是一种慢性疾病，具有用药时间长、疾病靶点多等特点。中医药在防治DR方面具有其独特的优势。因此，探讨防治DR方药的合理组方显得尤为重要。中医药理论具有模糊性和经验性，适合在宏观层面指导组方；代谢组学能灵敏、客观地反映机体整体状态，可作为客观连接方证的桥梁，适合剖析复方的组方规律。本项目首先采用代谢组学技术分析DR大鼠模型代谢物的时序性变化，结合视网膜内皮细胞损伤实验确定与DR疾病进程相关的一组关键差异代谢物。其次，采用定量代谢组学技术测定单味药及其组合、复方血栓通对DR关键差异代谢物调节作用的强弱，分析单味药作用的代谢通路，建立可预测药效的数学模型，定性、定量剖析复方血栓通的组方规律。以关键差异代谢物的含量趋于正常为目标，拟定新的复方并进行药效验证。既为临床防治DR的精准用药提供坚实的基础，也为基于整体观研究中医治疗慢性疾病的组方规律提供途径。

Diabetic retinopathy (DR) is a chronic disease that has a long duration of medication and a wide range of disease targets. Chinese medicine has its unique advantages in the prevention and treatment of DR. Therefore, it is necessary to investigate the rationality of prescription on DR. The integrity and empiricism of Chinese medicine theory makes it suitable for guiding the rational use of herbal formulas at the macroscopic level. Metabolomics can sensitively and objectively reflect physical conditions. Thus, it is well suited to study the regularity of compatibility. In our present study, the metabolomics will be used to analyze the temporal changes of endogenous metabolites in DR rats. Rat retinal vascular endothelial cells (RRCEC) will be used to validate DR-related key metabolites. Then the quantitative metabolomics technique will be used to determine the contents of those key metabolites after oral administration of single herbs or Fufang Xueshuangtong. Finally, a mathematical model will be established to predict the optimized prescription based on the metabolomics data from single herbs or Fufang Xueshuangtong. The optimized prescription will be validated both in metabolomics and pathophysiology. This study could lay a solid foundation for the precise use of medicines on DR in clinical, and provide a new strategy to investigate the rational use of herbal formulas based on the metabolomics.