目的 基于组分结构理论及网络药理学探究绿茶有效组分（奎尼酸、表儿茶素、没食子儿茶素、表没食子儿茶素、没食子儿茶素没食子酸酯和表没食子儿茶素没食子酸酯）干预年龄相关性黄斑变性（AMD）的最佳配伍结构及作用机制。方法 采用氯化钴致斑马鱼AMD模型，结合均匀设计法，以斑马鱼眼底血管异常生长的相对抑制率为评价指标，通过多元线性回归分析筛选绿茶有效组分干预AMD的最佳配伍结构；借助网络药理学预测其作用通路及关键靶点，并利用分子对接技术与实时荧光定量（qRT-PCR）法验证绿茶有效组分对关键靶点的调控作用。结果 当奎尼酸、表儿茶素、没食子儿茶素、表没食子儿茶素、没食子儿茶素没食子酸酯、表没食子儿茶素没食子酸酯的质量浓度分别为40、40、25、50、15、15 μg·mL^-1时干预AMD的药效最佳，其最佳配伍结构为8∶ 8∶ 5∶ 10∶ 3∶ 3；绿茶有效组分可能通过调控PI3K、Akt、TP53、HIF1A、VEGF等基因的表达，激活PI3K-Akt、HIF-1、Apoptosis和TNF信号通路，从而发挥干预AMD的药效作用。结论 绿茶有效组分可协同增效发挥干预AMD作用，且存在明确的最佳配伍结构，本研究为中药组分配伍规律研究提供思路，为绿茶干预AMD的组分新药研发奠定基础。

Objective To explore the optimal combination structure and mechanism of action of effective components of green tea (quinic acid, epicatechin, gallocatechin, epigallocatechin, gallocatechin gallate, and epigallocatechin gallate) in the intervention of agerelated macular degeneration (AMD) based on the theory of component structure and network pharmacology. Methods A zebrafish AMD model induced by cobalt chloride was used, combined with uniform design method. The relative inhibition rate of abnormal growth of zebrafish retinal vessels was taken as the dependent variable. The optimal combination structure of green tea effective components in the intervention of AMD was screened by multiple linear regression analysis. Network pharmacology was used to predict the action pathways and key targets, and molecular docking technology and real-time fluorescence quantitative (qRT-PCR) method were used to verify the regulatory effect of green tea effective components on key targets. Results When the mass concentrations of quinic acid, epicatechin, gallocatechin, epigallocatechin, gallocatechin gallate, and epigallocatechin gallate were 40, 40, 25, 50, 15, and 15 μg·mL^-1, respectively, the intervention effect on AMD was the best, and the optimal combination structure was 8∶ 8∶ 5∶ 10∶ 3∶ 3. Green tea effective components may exert the intervention effect on AMD by regulating the expression of genes such as PI3K, Akt, TP53, HIF1A, and VEGF, and activating the PI3K-Akt, HIF-1, Apoptosis, and TNF signaling pathways. Conclusion The effective components of green tea can exert a synergistic effect in the intervention of AMD, and there is a clear optimal combination structure. This study provides ideas for the research on the combination rules of traditional Chinese medicine components and lays a foundation for the development of new component drugs of green tea for the intervention of AMD.

R285.5

山东省重点研发计划项目（2021CXGC010511）；山东省科技型中小企业创新能力提升工程项目（2023TSGC0271）