黄连素逆转多重耐药鲍曼不动杆菌耐药性研究  

Study on the Reversal of Multidrug-resistance Acinetobacter Baumannii by Berberine

作　　者：周燿 李文杰 孙延文 骆丰[2] 林少华[2] ZHOU Yao;LI Wenjie;SUN Yanwen(School of Public Health,Zhejiang Chinese Medical University,Hangzhou(310053),China;The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine))

机构地区：[1]浙江中医药大学公共卫生学院,杭州310053 [2]浙江中医药大学附属第一医院(浙江省中医院)

出　　处：《浙江中医药大学学报》2025年第1期74-80,共7页Journal of Zhejiang Chinese Medical University

基　　金：浙江省中医药科技计划项目(2023ZL420)。

摘　　要：[目的]检测多重耐药鲍曼不动杆菌(multidrug-resistant Acinetobacter baumannii,MDRAB)对黄连素的敏感性,并研究黄连素对其耐药性的影响。[方法]收集浙江省中医院微生物室2023年1月至12月分离的MDRAB临床菌株60株,采用微量肉汤稀释法检测黄连素对MDRAB的最小抑菌浓度(minimum inhibitory concentration,MIC)。利用基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption ionization time-of-flight mass spectrometry,MALDI-TOF MS)对原代菌株和次代菌株进行蛋白质谱图分析,寻找黄连素作用后MDRAB质谱峰图是否出现差异峰谱;检测碳青霉烯酶相关基因表达情况,明确黄连素对MDRAB碳青霉烯酶表达的影响。[结果]60株MDRAB对黄连素的MIC值均大于或等于5 mg·mL^(-1)。黄连素作用后,应用MALDI-TOF MS分析两组菌株,发现质荷比6644.47、12297.67、16985.72处的峰是两组间差异较大的特征性峰,碳青霉烯酶亚胺培南金属-β-内酰胺酶(imipenemase metallo-β-lactamase,IMP)基因的检出率从34.2%下降到10.5%,差异有统计学意义(P<0.05)。[结论]黄连素单用时直接抑制或者杀灭MDRAB的能力非常有限;黄连素可通过改变MDRAB蛋白和碳青霉烯酶IMP基因的表达,逆转MDRAB的耐药机制,为临床治疗MDRAB感染提供新思路。[Objective Objective]To detect the sensitivity of multidrug-resistant Acinetobacter baumannii(MDRAB)to berberine and investigate the effect of berberine on its resistance.[Methods Methods]Sixty clinical strains of MDRAB obtained from Microbiology Laboratory of Zhejiang Provincial Hospital of Traditional Chinese Medicine between January and December 2023 were utilized.Microbroth dilution was used to measure the minimum inhibitory concentration(MIC)of berberine against MDRAB.Protein profiles of both the original and passaged strains were examined through matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS),carbapenemase related genes were detected simultaneously.[Results Results]The MIC values of 60 MDRAB strains to berberine were all more than or equal to 5 mg·mL^(-1).After the action of berberine,MALDI-TOF MS analysis of the two groups of strains revealed that the peaks at mass-to-charge ratios of 6644.47,12297.67,and 16985.72 were characteristic peaks with significant differences between the two groups.The detection rate of carbapenemase imipenemase metallo-β-lactamase(IMP)genes decreased from 34.2%to 10.5%,with a statistically significant difference(P<0.05).[Conclusion Conclusion]When used alone,berberine has very limited ability to directly inhibit or kill MDRAB;berberine can reverse the drug resistance mechanism of MDRAB by altering the expression of MDRAB proteins and IMP genes of carbapenemases,providing a new approach for the clinical treatment of MDRAB infections.

关 键 词：鲍曼不动杆菌 多重耐药 黄连素 耐药性 逆转 基质辅助激光解吸电离飞行时间质谱 特征峰 碳青霉烯酶 

分 类 号：R282[医药卫生—中药学]