没食子酸丙酯对抗真菌药体外抗丝状真菌活性的影响  

The effect of propyl gallate on the activity of various antifungal drugs against filamentous fungi in vitro

作　　者：徐岩[1] 庞广仁[1] 吕雪芳[1] 陈祖基[1] 孙声桃[1] 宋洁贞[1] 

机构地区：[1]河南省眼科研究所,郑州450003

出　　处：《中华眼科杂志》2006年第4期309-312,共4页Chinese Journal of Ophthalmology

基　　金：河南省自然科学基金资助项目(0311040500)

摘　　要：目的探讨没食子酸丙酯（PG）对抗真菌药体外抗丝状真菌活性的影响，为开发有效的眼科抗真菌药物提供实验依据。方法用微量液基稀释法测定两性霉素B（AMB）、特比奈芬（TBF）、布替奈芬（Bar）及酮康唑（KCZ）单独应用及与PG联合应用对6株眼科常见致病丝状真菌（茄病镰刀菌、串珠镰刀菌、梨孢镰刀菌、尖孢镰刀菌、烟曲霉菌、黄曲霉菌）及2株质控菌（白色念珠菌、近平滑念珠菌）的最低抑菌浓度（MIC）。将抗真菌药贮存液分别用1640液及PG-1640液稀释至2倍终浓度。将各浓度药液加入96孔微量板中，每孔100μl，再向各孔加入100μl菌液（最终菌浓度5×10^4CFU／m1），各种药物终浓度范围为0．0313～16μg／ml，含PG组PG的终浓度为400μg／ml。AMB的MIC终点判定标准是100％的真菌生长抑制，TBF、BTF、KCZ及PG的终点判定标准是约75％的真菌生长抑制。结果单纯应用PG400μg／ml对实验菌均无抗真菌活性。PG与AMB联合应用使AMB对茄病镰刀菌的抗菌活性增加8倍，对串珠镰刀菌、梨孢镰刀菌及烟曲霉菌的抗菌活性增加4倍，对尖孢镰刀菌、黄曲霉菌的抗菌活性增加2倍。PG与TBF联合应用使TBF对茄病镰刀菌的抗真菌活性增加32倍，对梨孢镰刀菌、尖孢镰刀菌的抗真菌活性增加4倍，对烟曲霉菌、黄曲霉菌的抗真菌活性增加2倍，但对串珠镰刀菌的抗菌活性有明显拮抗作用。PG与BTF联合应用使BTF对茄病镰刀菌的抗真菌活性增加32倍，但对其他实验菌无抗真菌协同作用，对串珠镰刀菌有明显拮抗作用。PG与KCZ联合应用，除对茄病镰刀菌的抗菌活性增加2倍外，对其他丝状真菌的抗菌活性均有明显拮抗作用。结论PG与AMB联合应用，对全部实验眼科致病丝状真菌均有明显抗真菌协同作用；PG与TBF联合应用，对部分实验菌有明显的抗真菌协同作用。Objective The influence of an antioxidant, propyl gallate （PG）, on the activity of amphotericin B （AMB）, terbinafine （TBF）, butenafine （BTF） and ketoconazole （KCZ） against ocular pathogenic filamentous fungi in vitro was investigated to determine whether PG could increase the antifungal activity. Methods Susceptibility tests were performed against 6 isolates of ocular pathogenic filamentous ftmgi （ Fusarium solanae, Fusarium moniliforme, Fusarium poae, Fusarium axysporum, AspergiUus fumigatus and AspergiUus flavus） and 2 quality control strains （ Candida kntsei ATCC 6258 and Cadida parapsilosis ATCC 22019） by the NCCLS M38-P broth microdilution method （MIC）. PG was added to the incubation media at a final concentration of 400 p.g/ml. Antifungal agents were serially two-fold diluted and final dilutions were made in 1640 and PG-1640 culture media to a concentration ranging from 0. 0313 to 16 μg/ml for AMB, TBF, BTF and KCZ. One hundred μl of the corresponding diluted inoculum suspension was added to each weU of the microdilution tray. The MIC end-point of AMB was determined as 100% growth reduction and the MIC end-point of TBF, BTF, KCZ and PG was determined as 75% growth reduction as compared with the turbidity produced by the control welL Results At a concentration of 400 μg/ml, PG did not show any antifungal activity under these experimental conditions. The combination of PG （400μg/ml） with amphotericin B revealed a remarkably increased activity against all of the isolates of ocular pathogenic filamentous fungi and quality control strains. In the combination of PG with terbinafine, a remarkably increased activity was observed against Fusarium solanae, Fusarium poae, Fusarium oxysporum, Aspergillus fumigatu and Aspergillus flavus. The combination of PG with butenafine had remarkably synergistic effect against Fusarium solanae, but did not synergistic or even showed antagonistic effect for other isolates. The combination of PG with ketaconazole was synergistic against Fusari

关 键 词：没食子酸丙酯 真菌 抗真菌药 微生物敏感性试验 

分 类 号：R772.21[医药卫生—眼科]