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作 者:韩蕾 仲华 王欣荣 王彦 HAN Lei;ZHONG Hua;WANG Xinrong;WANG Yan(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;School of Pharmacy,Naval Medical University,Shanghai 200433,China;Innovation Center for Medical Basic Research on Fungal Infectious Diseases,Ministry of Education,Shanghai 200433,China)
机构地区:[1]福建中医药大学药学院,福建福州350122 [2]海军军医大学药学系,上海200433 [3]真菌感染性疾病教育部医药基础研究创新中心,上海200433
出 处:《药学实践与服务》2024年第4期151-156,共6页Journal of Pharmaceutical Practice and Service
基 金:军队生物安全项目(20SWAQX29-1-6,145AHQ082021000X);国家自然科学基金(82204470)。
摘 要:目的 研究去甲泽拉木醛的体外抗真菌作用。方法 采用微量液基稀释法测定去甲泽拉木醛与氟康唑单独应用于23株真菌的最低抑菌浓度(MIC),以棋盘式微量液基稀释法测定两药联合抗耐药白念珠菌的协同指数(FICI),判断两药联合抗菌效果;并通过纸片扩散实验直观验证两药联合的协同作用。最后通过CCK-8法测定去甲泽拉木醛的细胞毒性。结果 去甲泽拉木醛单用时呈现广谱的抗真菌作用,MIC范围为4~32 g/L。两药联用时,可将氟康唑的有效浓度从大于64 g/L降至0.25 g/L,FICI值介于0.129~0.254之间,两药表现出协同抗耐药白念珠菌作用。CCK-8结果显示,去甲泽拉木醛在高于MIC值4倍浓度下才展示出细胞毒性。结论 去甲泽拉木醛表现出较好的抗真菌作用,与氟康唑联合时有很好的协同效果,且毒性较低。Objective To study the antifungal effect of demethylzelamaldehyde in vitro.Methods The minimum inhibitory concentrations(MIC)of demethylzeylasteral and fluconazole against 23 fungal strains were determined by micro liquid dilution method.The synergistic index(FICI)of the two drugs was determined using a checkerboard micro liquid dilution method.The synergistic effect of the combination of the two drugs was visually verified by paper diffusion experiments.Finally,the cytotoxicity of demethylzelamaldehyde was determined by CCK-8 method.Results Demethylzelamaldehyde showed a broad spectrum of antifungal activity when used alone,with MICs ranging from 4 g/L to 32 g/L.When combined with fluconazole,the effective concentration of fluconazole could be reduced from over 64 g/L to 0.25 g/L,with FICI values ranging from 0.129 to 0.254,indicating the synergistic effect of the two drugs.The CCK-8 results showed that demethylzeylasteral exhibited cytotoxicity only at concentrations four times higher than the MIC value.Conclusion Demethylzelamaldehyde exhibited good antifungal effect and synergistic effect with fluconazole,and its toxicity was low.
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