阿司匹林联合氟康唑对生物膜白念珠菌抑菌作用的研究  

Antifungal activity of aspirin in combination with fluconazole against Candida albicans biofilms

作　　者：阳隽[1] 张天托[1] 朱家馨[1] 黄静[1] 

机构地区：[1]中山大学附属第三医院呼吸内科,广州510630

出　　处：《中华检验医学杂志》2013年第6期569-572,共4页Chinese Journal of Laboratory Medicine

摘　　要：目的体外检测阿司匹林、氟康唑单用或联合对生物膜白念珠菌的抑菌活性，评价两药联合的抗菌效果。方法分别测定阿司匹林和氟康唑对生物膜白念珠菌的MIC50值，采用分级抑制浓度指数检测阿司匹林与氟康唑之间的抗菌作用关系。并应用荧光定量PCR检测分析阿司匹林对生物膜白念珠菌表面蛋白ALS3及HWP1表达的影响。结果阿司匹林对生物膜白念珠菌标准株ATCC64550，临床分离株14215、15346、15538及16335的MIC50分别为〉1440mg／L、〉1440mg/L、1440mg/L、720mg／L及1440mg／L，氟康唑对标准株及临床株生物膜白念珠菌的MIC50均〉64mg／L。联合用药对氟康唑耐药株ATCC64550作用增强不明显，对4株临床分离株分级抑制浓度（FIC）指数分别为0．75、0．5、0．75、0．75，表现为协同或相加作用。在阿司匹林作用下，与白念珠菌生物膜形成相关的表面蛋白ALS3和HWP1表达明显下降。结论阿司匹林能抑制白念珠菌生物膜的形成，可能促进生物膜白念珠菌对氟康唑的敏感性。Objective To assess antifungal activity of aspirin and fluconazole administered alone or in combination against Candida albicans biofilms in vitro, and to evaluate the combined effect of these two drugs. Methods The MIC50 of aspirin and fluconzole against biofilm-associated adherent cells were determined respectively, then the efficacy of combinations of aspirin and fluconazole were evaluated by calculating the fractional inhibitory concentration （FIC） index. The influence of aspirin on the mRNA expression of gene ALS3, HWP1 in biofilm cells were analyzed by fluorescent quantitative PCR assay. Results The MIC50 of aspirin for ATCC64550, clinical strains 14215,15346,15538,16335 were 〉 1440 nag/L, 〉 1440 mg/L, 1440 mg/L, 720 mg/L and 1440 mg/L respectively, the MIC50of flueonazole for biofilms cells of all the strains were 〉 64 mg/L. Aspirin did not enhance the antifungal effect of fluconazole against biofilm formed by ATCC64550, but synergistic and additive effects were found for the combination of aspirin and fluconazole to block the biofilm formation by clinical isolates （ FIC index = 0. 75, 0. 5, 0. 75, 0. 75 ）. Quantitative real-time PCR analysis showed aspirin could reduce the transcript level of ALS3 and HWP1. Conclusion Aspirin could inhibit C. albicans biofilm formation; it may increase the sensitivity of biofilm cells of C. albicans to fluconazole.

关 键 词：念珠菌 白色 生物膜 阿司匹林 氟康唑 

分 类 号：R978.1[医药卫生—药品]