双黄连注射剂成分与类过敏靶点的网络关联性分析  

Network Correlation Analysis Between Components of Shuanghuanglian Injection and Allergy-like Targets

作　　者：张伟龙 贺红 谯茹 贺鹏 李文姣 张良琦 刘晓轩 黄思琪 潘雪 贺福元 ZHANG Weilong;HE Hong;QIAO Ru;HE Peng;LI Wenjiao;ZHANG Liangqi;LIU Xiaoxuan;HUANG Siqi;PAN Xue;HE Fuyuan(School of Pharmacy,Hunan Provincial Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine,Supramolecular Mechanism and Mathematic-physics Chracterization for Chinese Materia Medica,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,中药成药性与制剂制备湖南省重点实验室,中医药超分子机理与数理特征化实验室,长沙410208

出　　处：《中国实验方剂学杂志》2024年第19期190-197,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81874507,82274215);湖南省重点研发计划项目(2022SK2014);湖南省自然科学基金和科药联合基金项目(2021JJ80058,2022JJ30453,2023JJ60124);湖南省教育厅项目(22B0379);长沙市自然科学基金项目(kq2208192)。

摘　　要：目的:基于网络药理学体系和中药复方定量谱学,建立一种以平衡常数为核心的拓扑网络分析方法,以探究双黄连注射剂(SHLI)中可能引起类过敏的成分群及其与网络靶点之间的作用关系。方法:72只SPF级SD雄性大鼠适应性喂养1周后,随机分为空白组、SHLI标准组、金银花组、黄芩组、连翘组与7组SHLI配比组(第1~7组),每组6只,对各组动物进行静脉滴注给药并在稳态后取血,建立各组试药及血浆成分的高效液相色谱法(HPLC)特征图谱,划分成分群并求算各组试药及血浆供试品中各成分群的峰面积变化值;采用酶联免疫吸附测定法(ELISA)测定动物血样中免疫球蛋白E(IgE)、组胺(HIS)、类胰蛋白酶(TPS)、总补体(CH50)和末端补体复合物(C5b-9)的类过敏指标变化情况;采用MATLAB R2020b v9.9.0软件计算各成分群与目标靶点的网络平衡常数及其构成矩阵的特征值,并根据其大小进行排序。结果:ELISA结果显示,与空白组比较,第1~3组IgE水平明显升高;第1~2组、第4~6组和SHLI标准组HIS水平明显升高;第4组CH50水平明显升高;第1组、第3~4组、金银花组和连翘组TPS水平明显升高;黄芩组C5b-9水平明显升高,差异均具有统计学意义(P<0.05)。根据色谱峰保留时间,在HPLC图谱上分为C1~C6共6个成分群。各成分群网络平衡常数大小排序为C6>C4>C1>C5>C3>C2,表明成分群C6对类过敏反应影响最大,最有可能为类致敏的反应原;特征值排序为C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS,表明成分群C2对于整个网络贡献度最大。结论:该研究基于SHLI成分群与类过敏靶点网络关联性分析,明确了成分群C6可能是双黄连注射剂中潜在的过敏原;成分群C2可能为药物作用机制的关键节点,可为中药注射剂致敏原的筛查提供新的策略和方法。Objective:Based on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine(TCM)compounds,a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection(SHLI),in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI.Method:After one week of adaptive feeding,72 SPFgrade SD male rats were randomly divided into blank group,SHLI standard group,Lonicerae Japonicae Flos(LJF)group,Scutellariae Radix(SR)group,Forsythiae Fructus(FF)group,and 7 groups of SHLI matching groups(groups 1-7),with 6 rats in each group.Rats in each group were administered the drug intravenously and blood samples were taken after steady state,high performance liquid chromatography(HPLC)characterization profiles of the testing drugs and plasma components in each group were established,and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified.Enzyme-linked immunosorbent assay(ELISA)was used to determine the changes of immunoglobulin E(IgE),histamine(HIS),tryptase(TPS),total complement(CH50)and terminal complement complex(C5b-9)in animal blood samples.MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets,and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values.Result:ELISA results showed that,compared with the blank group,groups 1-3 could significantly increase the IgE level,groups 1-2,groups 4-6 and SHLI standard group could significantly increase the HIS level,group 4 could significantly increase the CH50 level,groups 1,3-4,LJF group and FF group could significantly increase the TPS level,SR group could significantly increase the C5b-9 level,and the differences were all statistically significan(t P

关 键 词：双黄连 中药注射剂 类过敏反应 网络关联性 中药定量谱学 拓扑网络分析 高效液相色谱法(HPLC) 

分 类 号：R22[医药卫生—中医基础理论] TQ450.2[医药卫生—中医学] R28[化学工程—农药化工] O657[理学—分析化学]