基于MrgrpX2的双黄连注射剂中潜在成分虚拟筛选

陈莉 季文君 戴国英 陶渊达 周浩泽 杨袁

摘要 目的：运用计算机虚拟筛选技术，建立基于MrgrpX2的潜在类过敏成分的筛选模型，对双黄连注射液中13种成分进行虚拟筛选。方法：采用AutoDock Vina软件及LigPlot+软件，以MrgrpX2作为目标蛋白，对各单体成分进行虚拟分子对接筛选，计算受体和配体间的结合能并分析分子间作用类型。结果：分子对接的结果显示，13种单体成分的结合能依次为连翘酯苷A、黄芩苷、野黄芩苷、芦丁、连翘苷、黄芩素、木犀草素、隐绿原酸、新绿原酸、汉黄芩素、金丝桃苷、绿原酸和咖啡酸，分子间作用以Pi-Pi作用力、氢键作用和疏水作用为主。结论：建立的基于MrgrpX2的筛选模型可用于辅助潜在类过敏成分的初步筛选，筛选出的双黄连注射剂中的连翘酯苷A在这13种单体成分中与类过敏关键受体MrgrpX2具有更高的亲和力，提示可能有更高的致类过敏风险，值得深入研究。

关键词 类过敏;MrgrpX2;分子对接;双黄连注射剂;连翘酯苷A;隐绿原酸;新绿原酸;绿原酸

Virtual Screening Potential Anaphylactogens in Shuanghuanglian Injection Based on Mrgrpx2

CHEN Li，JI Wenjun，DAI Guoying，TAO Yuanda，ZHOU Haoze，YANG Yuan

（Department of Pharmacology，Suzhou Institute for Drug Control of Jiangsu Province，Suzhou 215104，China）

Abstract Objective：Using computer virtual screening technology，to establish a screening model of potential allergic components based on MrgrpX2 and to screen 13 components in Shuanghuanglian injection were virtually.Methods：AutoDock Vina software and LigPlot+software was used，with MrgrpX2 as the target protein.Virtual molecular docking screening of each monomer component was carried out，and the binding energy between the receptor and the ligand was calculated.The type of intermolecular interaction was analyzed.Results：The results of molecular docking showed that the binding energies of 13 monomer components were forsythin A，baicalin，scutellarin，rutin，forsythin，baicalein，luteolin，cryptochlorogenic acid，and neochlorogen.Acid，wogonin，hyperoside，chlorogenic acid and caffeic acid，the intermolecular interactions were mainly Pi-Pi interaction，hydrogen bond interaction and hydrophobic interaction.Conclusion：The established screening model based on MrgrpX2 can be used to assist the preliminary screening of potential allergy-like components.The selected forsythoside A in Shuanghuanglian Injection has higher levels of forsythin A in these 13 monomer components than the key allergic receptor MrgrpX2.Affinity indicates that there may be a higher risk of allergy-causing，and it is worthy of in-depth study.

Keywords Anaphylactoid reaction; MrgrpX2; Molecular docking; Shuanghuanglian Injection; Forsythoside A; Cryptochlorogenic acid; Neochlorogenic acid; Chlorogenic acid

中圖分类号：R242;R283文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.03.027

中药注射剂的急性过敏反应是其最常见的不良反应之一，是束缚中药注射剂进步的瓶颈。双黄连注射剂是由黄芩、金银花和连翘三味草药制备而成，具有清热解毒和抗菌消炎等作用，是临床常用药物[1-2]。然而随着其临床应用日益广泛，ADR报道亦日趋增多[3-4]。近年来双黄连注射剂多次被国家药品不良反应监测中心通报其引起的包括过敏反应[4-6]，因此建立针对过敏反应的灵敏可靠的非临床评价方法是目前亟须解决的问题。

急性过敏反应主要分为2个类别，一类是I型过敏反应，一类是类过敏反应[7]。与典型的过敏反应（I型过敏反应）不同，药物的类过敏反应直接引起肥大细胞或嗜碱性粒细胞脱颗粒，或激活补体系统间接引起该细胞释放生物活性递质，从而诱发一系列类过敏症状。有研究显示3/4的急性过敏反应为类过敏反应，发生率远高于典型的过敏反应[8]，并且由于类过敏反应在患者首次用药即可产生，严重的可为过敏性休克，直接威胁生命。但是目前对其发生机制却并不明确，也无标准的安全性评价模型，严重制约了中药注射剂的安全性及其质量控制水平。