葡萄糖酸亚铁及其与抗真菌药物联用对白念珠菌耐药性的影响研究

摘要/Abstract

摘要：

目的探讨葡萄糖酸亚铁单独使用及联用传统抗真菌药物对白念珠菌生物膜及其耐药性的影响。方法选用白念珠菌标准株及耐药株进行实验,分别制备菌株的浮游状态及生物膜状态。葡萄糖酸亚铁单独使用或与抗真菌药物联用处理白念珠菌,XTT减低法结合棋盘格稀释法检测抑制效果,时间-杀菌曲线测定药物对生物膜杀菌的动力学影响,扫描电镜观察白念珠菌生物膜形态。结果葡萄糖酸亚铁对浮游态及生物膜状态的白念珠菌标准株及耐药株均有抑制作用,50 mmol/L为其抑制白念珠菌标准株和耐药株生物膜50%活性的最低药物浓度(sessile minimal inhibitory concentration 50%,SMIC₅₀),和氟康唑联用有协同抑菌效果。时间-杀菌曲线结果显示,葡萄糖酸亚铁对白念珠菌标准株及耐药株生物膜的抑制作用随时间的延长或剂量的增加表现出增强的整体趋势,且联用药物的抑制效果较单独应用效果更明显。扫描电镜观察结果显示葡萄糖酸亚铁单独使用及联用药物均能有效抑制白念珠菌菌丝的生长和生物膜的形成。结论葡萄糖酸亚铁对白念珠菌标准株及耐药株生物膜存在抑制作用,可降低白念珠菌生物膜耐药性,与氟康唑联用表现为协同抗菌作用。

关键词: 白念珠菌, 葡萄糖酸亚铁, 抗真菌药物, 生物膜, 耐药性

Abstract:

Objective To investigate the effects of ferrous gluconate, both alone and in combination with conventional antifungal agents, on Candida albicans (C. albicans) biofilms and its drug resistance. Methods Experiments were conducted using standard strains and drug-resistant strains of C. albicans. Both the planktonic and biofilm states of the respective strains were cultured and established. C. albicans was treated with ferrous gluconate alone and in combination with antifungal drugs. The inhibitory effects were assessed using the XTT reduction assay and the checkerboard microdilution method respectively, while the time-kill curve tests were conducted to determine the kinetic effect of drugs on biofilm sterilization. The morphological changes of biofilms were observed under scanning electron microscopy (SEM). Results Ferrous gluconate exhibited inhibitory effects on both planktonic and biofilm states of standard strains and drug-resistant strains of C. albicans. The minimum drug concentration that inhibited 50% activity (SMIC₅₀) of biofilms was 50 mmol/L for both the standard and drug-resistant strains. A synergistic antifungal effect was observed when ferrous gluconate was combined with fluconazole. The time-kill curves for ferrous gluconate alone and in combination with fluconazole demonstrated that its inhibitory effect on the biofilms of both strains showed an overall trend of enhancement with the prolongation of time or the increase of dose, and the combination group exhibited a significantly stronger inhibitory effect compared to any agent used alone. Morphological observations revealed that both ferrous gluconate alone and in combination with antifungal drugs could reduce hyphal formation and biofilm-forming capacity of C. albicans. Conclusion Ferrous gluconate exerts an inhibitory effect on biofilms in both standard strains and drug-resistant strains of C. albicans and can reduce its drug resistance. The combination of ferrous gluconate and fluconazole demonstrates a synergistic antimicrobial effect.

Key words: Candida albicans, ferrous gluconate, antifungal agents, biofilm, drug resistance

中图分类号:

R781.5

熊雪宁, 陈婉婧, 袁玮煜, 王瑜菲, 朱书娴, 王牧天, 魏昕, 马鸣. 葡萄糖酸亚铁及其与抗真菌药物联用对白念珠菌耐药性的影响研究[J]. 口腔医学, 2026, 46(6): 448-454.

XIONG Xuening, CHEN Wanjing, YUAN Weiyu, WANG Yufei, ZHU Shuxian, WANG Mutian, WEI Xin, MA Ming. Effects of ferrous gluconate alone and combined with antifungal agents on Candida albicans resistance[J]. Stomatology, 2026, 46(6): 448-454.

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药物名称	标准株SMIC₅₀	耐药株SMIC₅₀
氟康唑	512.00	1 024.00
卡泊芬净	64.00	256.00
两性霉素B	0.50	2.00
特比萘芬	256.00	512.00
5-氟胞嘧啶	512.00	1 024.00

白念珠菌菌株	联用药物	FICI	结果
标准株	氟康唑	0.37	SYN
	卡泊芬净	0.75	IND
	两性霉素B	1.25	IND
	特比萘芬	1.03	IND
	5-氟胞嘧啶	0.63	IND
耐药株	氟康唑	0.42	SYN
	卡泊芬净	1.00	IND
	两性霉素B	1.25	IND
	特比萘芬	1.02	IND
	5-氟胞嘧啶	1.00	IND

白念珠菌菌株	联用药物	∑SYN	∑ANT	结果
标准株	氟康唑	242	-19	SYN(S)
	卡泊芬净	153	-173	IND
	两性霉素B	182	-43	SYN(M)
	特比萘芬	862	-13	SYN(S)
	5-氟胞嘧啶	282	-48	SYN(S)
耐药株	氟康唑	305	-181	SYN(M)
	卡泊芬净	218	-107	SYN(M)
	两性霉素B	17	-256	ANT(S)
	特比萘芬	14	-80	IND
	5-氟胞嘧啶	347	-39	SYN(S)