基于HEMT生物传感的抗组胺药物与MIF相互作用及验证研究  

Study on the interaction and validation of antihistamine drugs with MIF based on HEMT biosensing

作　　者：王静 吴志生[1,2] 赵小军 赵静[1] 郇星月 郭新雨 王恺怡 何晗 姚景春 关永霞 李市荣 张贵民 王逸飞 WANG Jing;WU Zhi-sheng;ZHAO Xiao-jun;ZHAO Jing;HUAN Xing-yue;GUO Xin-yu;WANG Kai-yi;HE Han;YAO Jing-chun;GUAN Yong-xia;LI Shi-rong;ZHANG Gui-min;WANG Yi-fei(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Engineering Research Center of Chinese Medicine Production and New Drug Development,Ministry of Education of People’s republic of China,Beijing 102488,China;State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 276005,China;Fangshan Hospital,Beijing University of Chinese Medicine,Beijing 102499,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]中药制药与新药开发教育部工程研究中心,北京102488 [3]经方与现代中药融合创新全国重点实验室,临沂276005 [4]北京中医药大学房山医院,北京102499

出　　处：《药物分析杂志》2024年第8期1348-1355,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家重点研发计划课题(2023YFC3504505);国家自然科学基金项目(82274110);国家医学攻关产教融合创新平台-中药智能制造工程平台项目(90010062820031);北京科技新星交叉项目(20230484458);中央高校基本科研业务费北京中医药大学揭榜挂帅项目(2022-JYB-JBZR-019,2022-JYB-JBZR-018);北京中医药大学横向课题(BUCM-2021-JS-FW-173)。

摘　　要：目的:建立生物传感技术集成模式生物斑马鱼研究方法,实现盐酸西替利嗪、盐酸非索非那定、咪唑斯汀、依巴斯汀4种抗组胺药物与过敏性鼻炎关键靶点巨噬细胞迁移抑制因子(MIF)相互作用及验证研究。方法:以砷化镓(AlGaAs/GaAs)高电子迁移率晶体管(HEMT)半导体材料为传感元件,MIF为生物元件,构建MIF-HEMT生物传感器,开展盐酸西替利嗪、盐酸非索非那定、咪唑斯汀、依巴斯汀与MIF相互作用的强度表征。进一步建立斑马鱼免疫炎症模型,记录空白组、模型组、阳性药组和低、中、高剂量药物组中性粒细胞迁移数目,计算药物炎症抑制率。结果:盐酸西替利嗪与MIF的结合能力最强,解离常数KD值达7.05×10^(-13)mol·L^(-1),盐酸非索非那定、咪唑斯汀、依巴斯汀与MIF作用的解离常数KD值分别为2.34×10^(-8)、1.94×10^(-7)和2.44×10^(-8)mol·L^(-1),均与MIF有结合作用。进一步采用斑马鱼免疫炎症模型进行验证,发现4种抗组胺药均能显著减少中性粒细胞迁移数量,其中100μmol·L^(-1)盐酸西替利嗪对中性粒细胞迁移抑制率达到68.5%。结论:本研究通过生物传感技术集成模式生物斑马鱼实验,实现了抗组胺药物与过敏性鼻炎关键靶点MIF相互作用研究,进一步验证了MIF是抗组胺药物发挥药效的潜在靶点,为药物疗效与作用靶点关联研究提供了重要参考。Objective:To establish an integrated model of biosensing technology for the study of zebrafish,and to study and verify the interaction between cetirizine hydrochloride,fexofenadine hydrochloride,mizolastine,and ebastine,with the key target of allergic rhinitis,macrophage migration inhibitory factor(MIF).Methods:A MIF-high electron mobility transistor(HEMT)biosensor was constructed using AlGaAs/GaAs HEMT as the sensing element and MIF as the biological element.The interaction strength between cetirizine hydrochloride,fexofenadine hydrochloride,mizolastine,and ebastine and MIF was characterized.Furthermore,a zebrafish immune inflammation model was established.The number of neutrophil migration in the blank control group,model group,positive drug group,and low,medium,and high-dose drug groups were recorded.And the drug inflammation inhibition rate were calculated.Results:Cetirizine hydrochloride exhibited the strongest binding ability to MIF,with a dissociation constant of 7.05×10-13 mol·L^(-1).The KD for the interactions between fexofenadine hydrochloride,mizolastine,and ebastine with MIF were 2.34×10-8 mol·L^(-1),1.94×10-7 mol·L^(-1)and 2.44×10-8 mol·L^(-1),respectively.All of them had binding effects with MIF.Further the validation using the zebrafish immune anti-inflammatory model revealed that all four antihistamines significantly reduced the number of neutrophil migrations,among which 100μmol·L^(-1)of cetirizine hydrochloride achieved a neutrophil migration inhibition rate of 68.5%.Conclusion:This study explores the interaction between antihistamines and the key protein target of AR through the integration of biosensing technology and zebrafish experiments.It was found that MIF is a potential target for antihistamine drugs to exert their pharmacological effects.It provides an important reference for research on drug efficacy and its association with targets.

关 键 词：HEMT生物传感器 巨噬细胞迁移抑制因子 过敏性鼻炎 盐酸西替利嗪 斑马鱼 

分 类 号：R917[医药卫生—药物分析学]