烟酰胺及联合伊曲康唑体外抗烟曲霉活性研究

中国真菌学杂志　 2022, Vol. 17 　Issue (2): 124-128.

烟酰胺及联合伊曲康唑体外抗烟曲霉活性研究

陈显振^1,2, 朱信霖^1,2, 姜伟伟^1,2, 扈东营^1,2, 张克明^1,2, 方文捷^1,2, 潘炜华^1,2, 刘晓刚^1,2, 廖万清^1,2

1. 海军军医大学第二附属医院皮肤科, 上海 200003;
2. 上海市医学真菌分子生物学重点实验室, 上海 200003

收稿日期:2022-01-05 出版日期:2022-04-28 发布日期:2022-05-07
通讯作者: 潘炜华,E-mail:panweihua9@sina.com;刘晓刚,E-mail:liuxiaogang67@126.com E-mail:panweihua9@sina.com;liuxiaogang67@126.com
作者简介:陈显振,男(汉族),硕士研究生在读.E-mail:cxz0109@126.com
基金资助:
国家自然科学基金重点项目（81720108026）；一带一路国际联合实验室（21410750500）

Study on antifungal activity of nicotinamide and the synergistic effect of nicotinamide to itraconazole against Aspergillus fumigatus in vitro

CHEN Xianzhen^1,2, ZHU Xinlin^1,2, JANG Weiwei^1,2, HU Dongying^1,2, ZHANG Keming^1,2, FANG Wenjie^1,2, PAN Weihua^1,2, LIU Xiaogang^1,2, LIAO Wanqing^1,2

1. Department of Dermatology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China;
2. Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai 200003, China

Received:2022-01-05 Online:2022-04-28 Published:2022-05-07

摘要/Abstract

摘要： 目的检测烟酰胺及联合伊曲康唑的抗烟曲霉活性。方法采用CLSI推荐的M38-A2肉汤稀释法及棋盘式微量液基稀释法检测烟酰胺与伊曲康唑对15株烟曲霉的最低抑菌浓度（MIC）和协同指数（FICI），通过荧光定量PCR检测加药后烟曲霉的相关基因表达水平。结果烟酰胺对烟曲霉具有抑制作用，MIC为12.8~25.6 mg/mL;烟酰胺与伊曲康唑具有协同抗菌作用，协同指数<0.5;膜蛋白相关基因与外排泵相关基因在烟酰胺单用及联合用药下，表达下调。结论烟酰胺具有抑制烟曲霉及增强伊曲康唑抗烟曲霉的作用，抑菌及增效作用与下调烟曲霉膜蛋白基因和外排泵基因表达有关。

关键词: 烟曲霉, 烟酰胺, 伊曲康唑, 联合治疗

Abstract: Objective To investigate the effect of nicotinamide (NAE) alone or in combination with itraconazole (ITR) against Aspergillus fumigatus. Methods We investigates the antifungal effects of ITR/NAE alone and in combination against 15 isolates of Aspergillus fumigatus according to the clinical and laboratory standards institute (CLSI) M38-A2. The minimum inhibitory concentrations (MICs) and the fractional inhibitory concentration index (FICI) were used to classify drug interactions. Real-time PCR was used to test the relative expression of gene in Aspergillus fumigatus treated with nicotinamide/itraconazole. Results Niacinamide had inhibitory effect on Aspergillus fumigatus, the MICs was 12.8-25.6 mg/mL. The FICI of the drugs in combination was less than 0.5, revealing synergism between NAE and ITR. The expression of membrane protein genes and efflux pump related genes was down-regulated under nicotinamide/itraconazole. Conclusions Nicotinamide inhibited Aspergillus fumigatus and enhanced itraconazole against Aspergillus fumigatus. This effect was related to the decrease of membrane protein and efflux pump protein gene expression of Aspergillus fumigatus.

Key words: Aspergillus fumigatus, nicotinamide, itraconazole, combined therapy

中图分类号:

R379.6

陈显振, 朱信霖, 姜伟伟, 扈东营, 张克明, 方文捷, 潘炜华, 刘晓刚, 廖万清. 烟酰胺及联合伊曲康唑体外抗烟曲霉活性研究[J]. 中国真菌学杂志, 2022, 17(2): 124-128.

CHEN Xianzhen, ZHU Xinlin, JANG Weiwei, HU Dongying, ZHANG Keming, FANG Wenjie, PAN Weihua, LIU Xiaogang, LIAO Wanqing. Study on antifungal activity of nicotinamide and the synergistic effect of nicotinamide to itraconazole against Aspergillus fumigatus in vitro[J]. Chinese Journal of Mycology, 2022, 17(2): 124-128.

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