孙相民 高华荣

[摘要] 目的 分析氟康唑聯合盐酸氨溴索对白色念珠菌影响及相关可能机制。 方法 依据药物敏感检测方案，使用微量稀释法来检测盐酸氨溴索与氟康唑单独使用和联合使用对耐药白色念珠菌与敏感白色念珠菌体外抗真菌影响，使用抑菌浓度指数与生长差异百分比模型对两种药物联合抗真菌影响要过进行评价;使用罗丹明6G当做氟康唑荧光代替物，流式细胞仪检测盐酸氨溴索对耐药白色念珠菌的药物转运泵影响情况。 结果 FICI评价联合用药抗白色念珠菌时，对CA8和CA4表征是无关，对CA16和CA10表征为协同;△E评价联合用药抗白色念珠菌时，对CA8和CA4表征是拮抗，对CA16和CA10表征是协同;在Rh6G吸收和Rh6G外排实验实验中，随着时间增加，盐酸氨溴索组荧光强度均高于对照组，且盐酸氨溴索外排量均低于对照组，差异有统计学意义（P<0.05）。 结论 氟康唑联合盐酸氨溴索对抵抗耐药白色念珠菌体外影响显著，其影响机制可能为盐酸氨溴索对抗真菌药物转运泵活性抑制有联系。

[关键词] 耐药白色念珠菌;氟康唑;盐酸氨溴索;协同作用

[中图分类号] R96          [文献标识码] A          [文章编号] 1674-0742（2018）08（c）-0125-03

Effect of Fluconazole and Ambroxol Hydrochloride on Candida Albicans

SUN Xiang-min， GAO Hua-rong

Department of Pharmacy， Peking University Medical Hospital， Zibo， Shandong Province， 255400 China

[Abstract] Objective To analyze the effects of fluconazole and ambroxol hydrochloride on Candida albicans and its possible mechanisms. Methods According to the drug sensitivity testing program， the microdilution method was used to detect the antifungal effects of ambroxol hydrochloride and fluconazole alone and in combination on resistant Candida albicans and Candida albicans in vitro. The antibacterial concentration index was used. The percentage of growth difference model evaluated the effect of the two drugs combined with antifungal; Rhodamine 6G was used as a substitute for fluconazole fluorescence， and the effect of ambroxol hydrochloride on the drug delivery pump of resistant Candida albicans was detected by flow cytometry . Results FICI evaluation of the combination of anti-Candida albicans against CA8 and CA4 characterization is irrelevant， CA16 and CA10 characterization of synergy; △ E evaluation of the combination of anti-Candida albicans against CA8 and CA4 antagonism， CA16 and CA10 characterization was synergistic; in the Rh6G uptake and Rh6G efflux experiments， the fluorescence intensity of the ambroxol hydrochloride group was higher than that of the control group over time， and the abundance of ambroxol hydrochloride was lower than that of the control group， with statistical significance （P<0.05）. Conclusion Fluconazole combined with ambroxol hydrochloride has a significant effect on resistance to Candida albicans in vitro. The mechanism may be related to the inhibition of antifungal drug transport pump activity by ambroxol hydrochloride.

[Key words] Resistance to Candida albicans; Fluconazole; Ambroxol hydrochloride; Synergy effect

近些年来，伴随着器官移植、恶性肿瘤及获得性免疫缺陷综合征患者逐年增多，免疫抑制剂与广谱抗菌药物广泛使用及患者机体内留置导管等技术快速发展，造成临床侵袭性真菌感染对患者发病与死亡率激增，尤其是念珠菌属与曲霉菌属所引发感染[1-4]。因此，该文通过分析氟康唑联合盐酸氨溴索对白色念珠菌影响，为临床真菌感染患者治疗提供一些借鉴。

1  资料与方法

1.1  实验材料

菌株为CA4、CA16、CA10及CA8（该院临床分离菌株），菌株都经过分离纯化，生理生化法鉴别，在﹣70℃冰箱内保存。……