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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(BTF)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(M IC)。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5×104CFU/m l),各种药物终浓度范围为0.0313~16μg/m l,含PG组PG的终浓度为400μg/m。lAMB的M IC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PG 400μg/m l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 To investigate the effect of propyl gallate (PG) on the antifungal activity of antifungal agents in vitro and to provide experimental evidence for the development of effective ophthalmic antifungal agents. Methods Micro-liquid-based dilution method was used to determine the effects of amphotericin B (AMB), terbinafine (TBF), butenafine (BTF) and ketoconazole (KCZ) Fusarium filamentous fungi (Fusarium solani, Fusarium moniliforme, Fusarium oxysporum, Fusarium oxysporum, Aspergillus fumigatus, Aspergillus flavus) and two control bacteria (Candida albicans, Candida parapsilosis) the lowest Bacteriostatic concentration (M IC). The antifungal stock solution was diluted to a 2-fold final concentration with 1640 solution and PG-1640 solution, respectively. Each concentration of the drug solution was added to a 96-well microplate, each well 100μl, and then added to each well 100μl of bacteria (final bacterial concentration 5 × 104CFU / ml), the final concentration of various drugs in the range of 0.0313 ~ 16μg / ml, containing PG The final concentration of group PG was 400 μg / m. The M IC endpoint of lAMB is 100% inhibition of fungal growth, and the endpoint of TBF, BTF, KCZ and PG is about 75% inhibition of fungal growth. Results The simple application of PG 400μg / ml had no antifungal activity against the experimental bacteria. The combination of PG and AMB increased the antibacterial activity of AMB against Fusarium solani by 8-fold, and the antibacterial activity against Fusarium moniliforme, Fusarium graminearum and Aspergillus fumigatus increased by 4-fold. The antibacterial activity against Fusarium oxysporum and Aspergillus flavus Activity increased by 2 times. The combined application of PG and TBF increased the antifungal activity of TBF against Fusarium solani by 32-fold and the antifungal activity against Fusarium oxysporum and Fusarium oxysporum by 4-fold. The antifungal activity against Aspergillus fumigatus and Aspergillus flavus Increased 2-fold, but Fusarium moniliforme antibacterial activity was significantly antagonistic effect. The combined application of PG and BTF increased the antifungal activity of BTF to Fusarium solani by 32-fold, but no antifungal synergism to other experimental bacteria and obvious antagonism to Fusarium moniliforme. PG and KCZ combined application, in addition to Fusarium solani antimicrobial activity increased 2-fold, other filamentous fungi antibacterial activity were significantly antagonistic effect. Conclusion PG combined with AMB has obvious antifungal synergistic effect on all experimental ocular pathogenic filamentous fungi. PG and TBF have obvious antifungal synergistic effect on some experimental bacteria.