目的 基于超分子“印迹模板”理论，首创因子旋转法与分子连接性指数（molecular connectivity index，MCI）耦合策略，系统解析活血化瘀中药的共性物质基础及其“结构-功能”关联机制，为中药质量标志物（quality markers，Q-Marker）筛选提供新范式。方法 采用UPLC法建立13味活血化瘀中药（川芎、丹参、桃仁、马鞭草、红花、延胡索、月季花、牛膝、益母草、三七、白芍、赤芍、当归）及3种经典复方（补阳还五汤、桃红四物汤、血府逐瘀汤）的指纹图谱，通过匹配频数法划分26个“印迹模板”成分簇作为结构性“物质单元”；利用因子旋转法对成分簇进行降维整合，提取6个功能性“物质单元”（累积方差贡献率88.37%），结合归一化评分评估给药性“物质单元”的综合效应；借助中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database，TCMSP）数据库计算MCI，量化成分簇结构相似性，并通过急性血瘀大鼠模型验证核心成分的药效贡献。结果 发现活血化瘀中药的“印迹模板”成分簇可划分为6个功能性“物质单元”，其中前3个功能性“物质单元”（累积贡献率66.85%）以黄酮类、生物碱类及萜类为核心，主导活血化瘀效应；补阳还五汤因黄酮类、生物碱类及萜类的高丰度匹配，综合评分（2.44）显著优于其他方剂，证实其“印迹模板”与靶点空间结构的最佳适配性；黄酮类、萜类、生物碱类的MCI相似度达0.988 7、0.970 1、0.940 7，且10个对照品与中药群体的一阶矩RSD仅1.794%，验证其“印迹模板”特征；动物实验证实，功能性“物质单元”可显著改善急性血瘀大鼠血液流变学指标（低切与中切全血黏度均显著降低，P＜0.01）及凝血功能［活化部分凝血酶原时间（activated partial thromboplastin time，APTT）显著延长，P＜0.01］。综合评分最高的给药性“物质单元”来源方剂（补阳还五汤组）在改善血液流变学及凝血功能的多个方面，效果均优于评分最低的来源（白芍组），体现多成分协同增效特性。结论 首次构建“个体-结构-功能-给药”四维解析体系，揭示黄酮类、生物碱类及萜类成分，通过超分子“印迹模板”动态识别机制，介导活血化瘀效应的核心途径。该研究为中药复杂体系的质量评价与作用模式解析提供了量化工具，推动中药现代化研究从“单一成分”向“结构簇协同”范式转变。

Objective Based on the supramolecular “imprinting template” theory, we developed the coupling strategy of factor rotation method and molecular connectivity index (MCI), systematically analyzed the common material basis and “structure-function” correlation mechanism of traditional Chinese medicine (TCM) for promoting blood circulation and removing stasis, and provided a new paradigm for screening quality markers (Q-Marker) of TCM. Methods UPLC was used to establish the fingerprint of 13 traditional Chinese herbs [Chuanxiong (Chuanxiong Rhizoma), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Taoren (Persicae Semen), Mabiancao (Verbenae Herba), Honghua (Carthami Flos), Yanhusuo (Corydalis Rhizoma), Yuejihua (Rosae Chinensis Flos), Niuxi (Achyranthis Bidentatae Radix), Yimucao (Leonuri Herba), Sanqi (Notoginseng Radix et Rhizoma), Baishao (Paeoniae Radix Alba, PRA), Chishao (Paeoniae Radix Rubra), Danggui (Angelicae Sinensis Radix)] for activating blood circulation and removing blood stasis and three classical compounds [Buyang Huanwu Decoction (补阳还五汤, BHD), Taohong Siwu Decoction (桃红四物汤), Xuefu Zhuyu Decoction (血府逐瘀汤)], and 26 “imprinting template” component clusters were divided as structural “material units” by matching frequency method. The factor rotation method was used to reduce the dimension of the component cluster, and six functional “material units” were extracted (the cumulative variance contribution rate was 88.37%). Combined with the normalization score, the comprehensive effect of the drug “material units” was evaluated. The MCI was calculated by TCMSP database, the structural similarity of component clusters was quantified, and the contribution of core components to drug efficacy was verified by an acute blood stasis rat model. Results The “imprinting template” component cluster of traditional Chinese medicine for promoting blood circulation and removing blood stasis could be divided into six functional “material units”, of which the first three functional unit (66.85%) was dominated by flavonoids, terpenoids, and alkaloids. Due to the high abundance of flavonoids, terpenoids and alkaloids, the comprehensive score (2.44) of BHD was significantly better than that of other prescriptions, which confirmed the best fit between its “imprinting template” and the spatial structure of the target. The MCI similarity of flavonoids, terpenoids and alkaloids was 0.988 7, 0.970 1, 0.940 7, and the first moment RSD of 10 reference substances and traditional Chinese medicine group was only 1.794%, which verified their “imprinting template” characteristics. Animal experiments confirmed that functional “material unit” could significantly improve hemorheology (whole blood viscosity decreased significantly in low cut and middle cut, P < 0.01) and coagulation function (APTT prolonged significantly, P < 0.01) in rats with acute blood stasis. BHD, which ranked the highest in the normalized score of “substance unit”, improved hemorheology and coagulation function better than PRA, which reflected the synergistic effect of multi-components. Conclusion This study establishes a four-dimensional analysis system of “individual-structure-function-drug delivery” for the first time, and reveals the core mechanism by which flavonoids, terpenoids and alkaloids play the role of promoting blood circulation and removing blood stasis through dynamic recognition of the macromolecular “imprinting template”. This study provided a quantitative tool for the quality evaluation and action mode analysis of the complex system of traditional Chinese medicine, and promoted the transformation of the research on traditional Chinese medicine modernization from “single component” to “structure cluster synergy” paradigm.

国家自然科学基金项目（82274215）；湖南省重点研发计划项目（2022SK2014）；湖南省自然科学基金项目（2022JJ30453）；湖南中医药大学2022年度校级“揭榜挂帅”专项（2022-12-27-1）；湖南省自然科学基金青年项目（2021JJ40398）