中药单体与抗菌药物联合应用对抗泛耐药鲍曼不动杆菌的作用研究  

Research on the Effects of Traditional Chinese Medicine Monomer Combined with Antibacterial Drugs Against Extensively Drug Resistant Acinetobacter baumannii

作　　者：彭勤 凌保东[1,2] 蔺飞[3] 袁浩宇 王清会[1,2] 孟千琳 陈浩 Peng Qin;Ling Baodong;Lin Fei;Yuan Haoyu;Wang Qinghui;Meng Qianlin;Chen Hao(Sichuan Province College Key Laboratory of Structure-Specifific Small Molecule Drugs,Chengdu Medical College,Chengdu 610500;School of Pharmacy,Chengdu Medical College,Chengdu 610500;The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500;Nuclear Industry 416 Hospital,Chengdu 610500)

机构地区：[1]成都医学院结构特异性小分子药物研究四川省高校重点实验室,成都610500 [2]成都医学院药学院,成都610500 [3]成都医学院第一附属医院,成都610500 [4]核工业四一六医院,成都610500

出　　处：《中药药理与临床》2020年第2期140-145,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:81373454)。

摘　　要：目的:研究中药单体槲皮素二水物、盐酸小檗碱、黄芩苷3种中药单体对泛耐药鲍曼不动杆菌(XDRAB)生物被膜形成能力及粘附作用的影响,并探讨以上3种中药单体分别与4种特殊使用级抗菌药物(亚胺培南、美罗培南、替加环素、多粘菌素)联合应用对抗XDRAB的协同效应。方法:应用微量肉汤稀释法检测槲皮素二水物、盐酸小檗碱、黄芩苷3种中药单体和15种抗菌药物对9株XDRAB的最低抑菌浓度(MIC),结晶紫染色法和平板菌落计数法检测3种中药单体对XDRAB生物被膜形成能力和粘附能力的影响,微量棋盘稀释法检测中药单体槲皮素二水物、盐酸小檗碱、黄芩苷分别与亚胺培南、美罗培南、替加环素、多粘菌素B联合应用的协同抗菌效应。结果:槲皮素二水物、盐酸小檗碱、黄芩苷对XDRAB的MIC分别为512μg/ml、256μg/ml、1024μg/ml,除多粘菌素B和替加环素以外,9株XDRAB对13种抗菌药物均耐药;槲皮素二水物、盐酸小檗碱、黄芩苷分别在64μg/ml、32μg/ml、128μg/ml的浓度下抑制XDRAB生物被膜的形成以及对导尿管的粘附。与模型对照组相比,3种中药单体分别与亚胺培南、美罗培南、替加环素联用时,中药单体与抗菌药物的MIC均下降,表现为不同程度的协同作用。结论:槲皮素二水物、盐酸小檗碱、黄芩苷3种中药单体不仅能抑制XDRAB生物被膜的形成能以及对医用材料的粘附,而且与分别与亚胺培南、美罗培南、替加环素联用后对XDRAB的抗菌活性有不同程度的协同作用。Objective: To study the effects of Traditional Chinese Medicine monomers(TCMM):quercetin dihydrate, berberine hydrochloride and baicalin on the biofilm formation and adhesion to Acinetobacter baumannii(XDRAB) strains,and explore its synergistic antibacterial effects when combined with 4 special-purpose antibacterial drugs(imipenem,meropenem, tigecycline, polymyxinB). Methods:Minimal inhibitory concentration(MIC) against 9 XDRAB strains of three TCMMs and15 antibacterial drugs were detected by micro-broth dilution method. Crystal violet staining and plate colony counting method were used to assess effects of TCMMs(quercetin dihydrate,berberine hydrochloride,and baicalin) on biofilm formation and adhesion to XDRAB.The synergistic effects of 3 TCMMs combined with imipenem,meropenem, tigecycline adn polymyxinB were tested by micro-board dilution method. Results:The MICs of TCMMs(quercetin dihydrate,berberine hydrochloride and baicalin)were 512 μg/ml, 256 μg/ml, and 1024 μg/ml respectively. Except for polymyxin B and tigecycline,9 XDRAB strains were resistant to other 13 antibacterial drugs. TCMMs(quercetin dihydrate, berberine hydrochloride and baicalin) inhibited the biofilm formation and adhesion to the catheter of 9 XDRAB strains at doses of 64 μg/ml,32 μg/ml and 128 μg/ml respectively. Compared with the model group,when TCMMs combined with imipenem,meropenem and tigecycline separately, different degrees of synergistic effects were observed, MICs of TCMMs and antibacterial drugs were reduced.Conclusion:TCMMs(quercetin dihydrate,berberine hydrochloride and baicalin)could inhibit the biofilm formation and the adhesion to medical materials of XDRAB. When above TCMMs combined with imipenem,meropenem and tigecycline respectively, there may be different degrees of synergistic effects.

关 键 词：中药单体(槲皮素二水物、盐酸小檗碱、黄芩苷) 泛耐药鲍曼不动杆菌 生物被膜 细菌粘附 联合用药 

分 类 号：R965[医药卫生—药理学]