基于斑马鱼模型的5种甘草酸类药物心脏保护作用评价  

Cardiovascular activity of five glycyrrhizic acid drugs based on zebrafish model

作　　者：李伟 李晓彬 董宇晴 于淑晴 陈红斗 张驰 陆伟 杨晴晴 LI Wei;LI Xiaobin;DONG Yuqing;YU Shuqing;CHEN Hongdou;ZHANG Chi;LU Wei;YANG Qingqing(Department of Pharmacy,Nanjing Drum Tower Hospital Group Suqian Hospital,Suqian 223800,China;Department of Pharmacy,Suqian Hospital Affiliated to Xuzhou Medical University,Suqian 223800,China;Biology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250103,China;Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province,Jinan 250103,China;Department of Nephrology,Nanjing Drum Tower Hospital Group Suqian Hospital,Suqian 223800,China)

机构地区：[1]南京鼓楼医院集团宿迁医院药学部,江苏宿迁223800 [2]徐州医科大学附属宿迁医院药学部,江苏宿迁223800 [3]齐鲁工业大学(山东省科学院)山东省科学院生物研究所,山东济南250103 [4]山东省人类疾病斑马鱼模型与药物筛选工程技术研究中心,山东济南250103 [5]南京鼓楼医院集团宿迁医院肾内科,江苏宿迁223800

出　　处：《药物评价研究》2024年第9期1995-2005,共11页Drug Evaluation Research

基　　金：江苏省中药骨干人才高级研修项目(苏中医科教[2022]17号);宿迁市科技计划资助项目(K202203);徐州医科大学附属医院发展基金项目(XYFY202237)。

摘　　要：目的利用斑马鱼模型评价异甘草酸镁注射液、甘草酸二铵注射液、复方甘草酸苷片、甘草酸二铵肠溶胶囊和注射用复方甘草酸单铵S 5种甘草酸类药物制剂的心脏保护作用。方法利用正常发育至受精后48 h的心脏荧光转基因斑马鱼作为实验动物,将斑马鱼随机分为对照组、阳性对照组、模型组和不同浓度甘草酸制剂样品组。在24孔板里分别给予不同浓度样品、阳性对照药物和造模药物,加培养水至2 mL后,置于(28±5)℃恒温光照培养箱让胚胎继续发育。24 h后,用培养水清洗斑马鱼,置于荧光倒置显微镜下观察斑马鱼心律变化并拍照。其中抗心律失常活性的阳性药为丹红注射液(9μL·mL^(-1)),造模药为特非那定(15μg·mL^(-1)),统计斑马鱼1 min的心率及静脉窦和动脉球之间的距离(SV-BA)。抗心衰活性的阳性药为地高辛(0.1μg·mL^(-1)),造模药品为阿霉素(60μmol·L^(-1)),统计斑马鱼1 min的心率、心包面积、心室短轴缩短率、每搏输出量及射血分数。结果甘草酸二铵肠溶胶囊、注射用复方甘草酸单铵S及异甘草酸镁注射液有较好的抗心律失常活性,注射用复方甘草酸单铵S具有较好的抗心衰活性。结论5种甘草酸制剂在抗心律失常和抗心衰方面具有不同程度活性,可为开发甘草酸类药物在心脏保护方面的适应症提供理论依据。Objective To evaluate the cardioprotective effects of five glycyrrhizic acid drugs:Magnesium Isoglycyrrhizinate Injection,Diammonium Glycyrrhizinate Injection,Compound Glycyrrhizin Tablets,Diammonium Glycyrrhizinate Enteric-coated Capsules and Compound Monoammonium Glycyrrhizinate S for Injection using zebrafish model.Methods Zebrafish with fluorescent transgenic heart from normal development to 48 h after fertilization were randomly divided into blank group,positive control group,model group and glycyrrhizic acid preparation sample group with different concentrations.Samples of different concentrations,positive control drugs and modeling drugs were given in 24-well plates,and 2 mL of culture water was added,then the embryos were placed in a(28±5)℃ constant temperature light incubator for continued development.After 24 h,zebrafish were cleaned with culture water and placed under inverted fluorescence microscope to observe the change of heart rate.Among them,Danhong Injection(9μg·mL^(-1))was the positive drug for antiarrhythmic activity,and terfenadine(15μg·mL^(-1))was the modeling drug.The heart rate of Zebrafish within 1 min and the distance between Sinus vena and bulb arterial(SV-BA)were analyzed statistically.The control drug for anti-heart failure activity was digoxin(0.1μg·mL^(-1)),and the modeling drug was doxorubicin(60μmol·L^(-1)).The heart rate,pericardial area,ventricular brachyaxis shortening rate,stroke output and ejection fraction of zebrafish within 1 min were statistically analyzed.Results Under the experimental conditions,Diammonium Glycyrrhizinate Enterocapsule Capsule,Compound Monoammonium Glycyrrhizinate S for Injection and Magnesium Isoglycyrrhizinate Injection have better antiarrhythmia activity,and compound monoammonium glycyrrhizinate S for injection has better anti-heart failure activity.Conclusion These five glycyrrhizic acid drugs have different activities in anti-arrhythmia and anti-heart failure.This study can provide theoretical basis for developing the indications of these

关 键 词：甘草酸类药物 斑马鱼 抗心律失常 抗心衰 心脏保护 异甘草酸镁注射液 甘草酸二铵注射液 复方甘草酸苷片 甘草酸二铵肠溶胶囊 注射用复方甘草酸单铵S 

分 类 号：R285[医药卫生—中药学]