目的 系统分析并识别瓜蒌薤白汤主要化学成分和入血成分，预测其防治冠心病的药效物质基础和作用机制。方法 采用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱（UHPLC-Q-Orbitrap HRMS）进行瓜蒌薤白汤体内外成分分析，结合色谱峰保留时间、精确相对分子质量、碎片离子、中性丢失等信息进行化合物指认。使用生物信息学方法，对潜在靶点进行GO和KEGG富集分析，借助Cytoscape软件构建瓜蒌薤白汤“活性成分-核心靶点-通路”网络图，对潜在活性成分和作用通路进行预测。利用AutoDock Tools 1.5.6软件对其活性成分与核心靶点进行分子对接验证。结果 瓜蒌薤白汤体外定性得到了68个化学成分，大鼠ig给药后在血清样本中检测到23个入血成分。其中芹菜素、木犀草素、酒渣碱、亚油酸等化合物为瓜蒌薤白汤发挥治疗冠心病药效的关键成分，前列腺素内过氧化物合成酶2（prostaglandin-endoperoxidesynthase 2，PTGS2）、肿瘤坏死因子（tumor necrosis factor，TNF）、基质金属蛋白酶-9（matrix metalloproteinase-9，MMP-9）、表皮生长因子受体（epidermal growth factor receptor，EGFR）、半胱氨酸蛋白水解酶3（cysteine-containing aspartate-specific protease 3，CASP3）等为瓜蒌薤白汤治疗冠心病的主要靶点，涉及到脂质与动脉粥样硬化、癌症的途径、TNF信号通路、NF⁃κB信号通路、MAPK信号通路。结论 初步鉴定了瓜蒌薤白汤防治冠心病的潜在药效成分并预测其作用靶点，为该方药效物质基础及作用机制的深入研究提供参考。

Objective To systematically analyze and identify chemical constituents of Gualouxiebai Decoction, and predict the pharmacological basis and mechanism of its prevention and treatment of coronary heart disease. Methods Gualouxiebai Decoction and drug-containing serum were analyzed by UHPLC-Q-Orbitrap HRMS, and the identification of in vivo and in vitro components were carried out with retention time, precise molecular weight, fragment ions and neutral loss. Bioinformatics methods were used to enrich the GO and KEGG pathways of potential targets. The network diagram of "active component-key target-pathway" of Gualouxiebai Decoction was constructed with Cytoscape 3.7.2 to predict potential active ingredients and pathways. AutoDock Tools 1.5.6 was used to verify the molecular docking between active ingredients and core targets. Results A total of 68 chemical components were identified in vitro, and 23 components were detected in serum samples of rats after gaved Gualouxiebai Decoction. Among them, apigin, luteolin, leae alkaloid, linoleic acid and other compounds are the key components of Gualouxiebai Decoction in the treatment of coronary heart disease, and PTGS2, TNF, MMP9, EGFR, CASP3 are the main targets. It involves the pathways of lipid and atherosclerosis, pathways in cancer, TNF signaling pathway, NF-κB signaling pathway and MAPK signaling pathway. Conclusion This study preliminarily identified the potential effective components of Gualouxiebai Decoction in the prevention and treatment of coronary heart disease, and predicted the target of action, providing a reference for the further study of the pharmacodynamic substance basis and action mechanism of this prescription.

R284.1

河南省重点研发与推广专项（科技攻关）（202102310187）；国家重点研发计划资助项目（2021YFC2401105）；河南省中青年卫生健康科技创新优秀青年人才培养项目（YXKC2020058）；国家自然科学基金资助项目（82003921）