摘要
目的预测和观察穿心莲内酯总磺化物(AS)联合头孢西丁(FOX)对耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)的联合抑制作用。方法采用网络药理学预测AS联合FOX对MRSA的作用机制;微量稀释法测定AS、FOX对MRSA的最小抑菌浓度;棋盘法测定两药联用对MRSA的分数抑制浓度指数、确定最佳抑菌浓度比;微孔板法检测给药后MRSA的成熟期细菌生物膜(BF)内活菌数的变化。结果AS联合FOX针对MRSA的共同作用点是MRSA毒力因子Hla和PVL,另外AS也作用于BF相关分子FnbB。AS和FOX对MRSA的MIC分别为50mg·mL-1和32μg·mL-1;最佳抑菌浓度比为25mg·mL-1AS+4μg·mL-1FOX,FICI值=0.625,表现为相加作用;FOX(16、8、4μg·mL-1)单独作用后成熟MRSA BF内活菌数无明显抑制,AS(25、12.5mg·mL-1)单独或联合FOX(16、8、4μg·mL-1)作用后成熟MRSA BF内活菌数均减少(P<0.01)。结论AS联合FOX干预MRSA有增效作用,与抑制MRSA BF有关,AS与抗生素联用是治疗MRSA感染的潜在有效方案。
OBJECTIVE To predict and observe the synergistic inhibitory effect of andrographolide total sulfonate(AS)with cefoxitin(FOX)on methicillin-resistant Staphylococcus aureus(MRSA).METHODS The effect mechanism of AS with FOX on MRSA was predicted by network pharmacology technique.The minimum inhibitory concentration(MIC)of AS and FOX on MRSA was determined by broth dilution method.The chessboard method was used to determine the fractional inhibition concentration index(FICI)of MRSA and the optimal inhibitory concentration ratio.MRSA was cultured on 96-well plates and the effects of AS and FOX on mature biofilm(BF)were studied using an XTT reduction assay.Changes in the amount of living bacteria were determined with a microplate reader 24 h after treatment.RESULTS The common targets of AS with FOX against MRSA were MRSA virulence factors Hla and PVL.AS also acted on bacterial BF-related molecule FnbB.The MICs of AS and FOX for MRSA were 50 mg/mL and 32μg/mL,respectively.The optimal inhibitory concentration ratio was 25 mg/mL AS+4μg/mL FOX,FICI value=0.625,which showed additive effect.The number of viable bacteria in mature MRSA BF was not inhibited by FOX(16,8,4 ug/mL),but decreased by AS(25,12.5 mg/mL)alone or combined with FOX(16,8,4 ug/mL).CONCLUSION AS with FOX has the synergistic effect on MRSA,which is related to inhibiting MRSA BF.AS combined with antibiotics might be a potential effective treatment for MRSA infection.
作者
张璐璐
包梅
杨伟峰
吕诚
肖诚
官福兰
易剑峰
李立
吕朗
王毅
谭勇
Zhang Lulu;Bao Mei;Yang Weifeng;Lv Cheng;Xiao Cheng;Guan Fulan;Yi Jianfeng;Li Li;LvLang;Wang Yi;Tan Yong(School of Chemical and Biological Engineering,Yichun University,Yichun,336000,China;Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing,100700,China;Experimental Research Certer,China Academy of Chinese Medical Science,Beijing,100700,China;Institute of Clinical Medicine,China-Japan Friendship Hospital,Beijing,100029,China;Department of Pharmacology,School of Medicine,Yale University,New Haven,CT06520,USA;State Key Laboratory of Innovative Natural Medicine and Traditional Chinese Medicine Injections,Ganzhou,341000,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2020年第7期2556-2562,共7页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家科学技术部国家科技重大专项(2008ZX10101001-005-003):“一带一路”传染病中医药临床诊疗方案推广应用,负责人:吕诚
国家科学技术部创新天然药物与中药注射剂国家重点实验室开放课题项目(QFSKL2018003):穿心莲内酯与抗生素联合增效减毒分子机制研究,负责人:谭勇
中国中医科学院中央级公益性科研院所基本科研业务费专项资金资助项目(Z0558):喜炎平对抗支原体肺炎治疗中阿奇霉素耐药的生物标志研究,负责人:谭勇
关键词
穿心莲内酯
头孢西丁
耐甲氧西林金黄色葡萄球菌
协同抑菌作用
Andrographolide
Cefoxitin
Methicillin-resistant staphylococcus aureus
Synergistic antibacterial effect
