马桑水提取物抗耐甲氧西林金黄色葡萄球菌的作用机制研究  

Mechanism of Coriaria sinica extract on anti-methicillin resistant Staphylococcus aureus

作　　者：黄德斌[1] 胡泽华[1] 余昭芬[1] 黄谨[1] 陈薛妃 

机构地区：[1]湖北民族学院医学院,湖北恩施445000

出　　处：《中草药》2017年第9期1802-1811,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81360654)

摘　　要：目的探索马桑水提取物(CSE)对耐药金黄色葡萄球菌(MRSA)的抗菌作用机制。方法分别用AFFX原核表达谱芯片、Western-blotting、SDS-PAGE凝胶电泳等方法,测定CSE对MRSA相关基因表达、自溶酶以及β-内酰胺酶的影响。结果 MRSA对绝大多数抗生素耐药,而CSE与多种β-内酰胺类抗生素合用具有显著地协同效应(P<0.05);可显著下调MRSA的RNA表达总量,单用CSE或与氨苄西林合用均能呈剂量依赖性调控基础代谢基因、肽聚糖水解酶(lytM)基因、转运子基因、青霉素结合蛋白(PBPs)以及β-内酰胺酶活性(P<0.05);可显著提高MRSA菌体内头孢唑啉浓度(P<0.05)。结论 CSE具有抑制MRSA作用,与β-内酰胺类抗生素合用具有协同作用。其机制与调控ribA、PBPs、lytM等相关靶基因的表达与转录,影响药物主动外排、细菌自溶及代谢等多种因素有关。Objective To explore the synergies mechanism of Coriaria sinica extract（CSE） combined with β-lactam antibiotics on methicillin resistant Staphylococcus aureus（MRSA）. Methods The relevant gene expression, autolytic enzyme, and influence of β-lactamase were determined by AFFX prokaryotic expression microarray, Western-blotting, SDS-PAGE gel electrophoresis, etc. Results MRSA was resistant to the most antibiotics, and it had significant synergistic antibacterial effect while CSE was combined with β-lactam antibiotics（P 〈0.05）. The CSE can significantly reduce the total expression of RNA and regulate the expression of many genes with showing a dose-dependence when used alone or combined with ampicillin（AP）, such as the basal metabolism genes, peptidoglycan hydrolase gene（lytM）, transporter gene, PBPs, β-lactamase activity, etc.（P 0.05）. It can significantly improve the concentration of cefotaxime（CFX） in internal of MRSA（P 〈0.05）. Conclusion The CSE has significant inhibitory effects on MRSA, and it has significant synergistic effects when combined with β-lactam antibiotic on MRSA. The mechanism is associated with many factors of MRSA, such as regulation of expression and transcription on target genes（ribA, PBPs, lytM, etc.）, the influence of active efflux, autolysis and metabolism, etc.

关 键 词：马桑水提取物 Β-内酰胺类抗生素 耐药金黄色葡萄球菌 青霉素结合蛋白 协同效应机制 

分 类 号：R285.5[医药卫生—中药学] R378.1[医药卫生—中医学]