白色、光滑假丝酵母菌氟康唑耐药株的体外诱导及与Sho1、Yap1基因的关系  

Study of Candida albicans and Candida glabrata Resistance to Fluconazole and its relationship of Sho1 and Yap1 Gene Expression

作　　者：黄金梅 陈旭艳 李华 董志高 范薇 田丽红 HUANG Jin-mei;CHEN Xu-yan;LI Hua;DONG Zhi-Gao;FAN Wei;TIAN Li-hong(Depa rtment of Hematology and Rheumatology,The Second Affiliated Hospital of Xiamen Medical College,Xiamen 361021,Fujian,China)

机构地区：[1]厦门医学院附属第二医院血液风湿科

出　　处：《海峡药学》2019年第12期26-29,共4页Strait Pharmaceutical Journal

基　　金：福建省卫计委青年科研课题(项目编号:2016-2-69)

摘　　要：目的体外诱导白色、光滑假丝酵母菌氟康唑耐药株,检测耐药株耐药相关基因Sho1、Yap1的表达情况,探讨Sho1、Yap1与白色、光滑假丝酵母菌对氟康唑耐药的关系。方法先以MTT微量液基稀释法检测白色、光滑假丝酵母菌对氟康唑的药敏性,再用氟康唑浓度递增法体外诱导其耐药株,并用实时荧光定量PCR法检测耐药株与野生株耐药相关基因Sho1、Yap1的表达水平。结果白色、光滑假丝酵母菌耐药株与野生株都有Sho1、Yap1基因表达,而耐药株Sho1、Yap1基因表达水平明显升高,耐药株与野生株有显著差别(P<0.05)。白色假丝酵母菌氟康唑耐药株Sho1、Yap1的表达量分别是其野生株的3.09、4.32倍;光滑假丝酵母菌氟康唑耐药株Sho1、Yap1的表达量分别是其野生株的7.14、100.88倍。结论白色、光滑假丝酵母菌对氟康唑耐药可能与Sho1、Yap1基因过度表达有关,氟康唑可诱导信号传导相关基因过表达,从而产生耐药性。OBJECTIVE To induce the resistant strains of Candida albicans and Candida glabrata to fluconazole in vitro and investigate the relationship of related drug resistance gene expression.METHODS Susceptibility of Candida albicans and Candida glabrata to fluconazole was evaluated by a standard broth microdilution method.The resistant strains were induced with consecutive increasing concentration of fluconazole in vitro.The expression levels of drug-resistant related genes were measured by real-time PCR.RESULTS Sho1 and Yap1 mRNA expressions were found in both fluconazole resistant strains and wild strains of Candida albicans and Candida glabrata.Compared to the wild strains,mRNA expression level of Sho1 and Yap1 was higher in fluconazole resistant strains(P<0.05).mRNA expression level of Sho1 and Yap1 was 3.09 times higher and 4.32 times higher than wild strain respectively in Candida albicans,but 7.14 times higher and 100.88 times higher respectively in Candida glabrata.CONCLUSION The overexpression of the Sho1 and Yap1 mRNA was found in the strains of Candida albicans and Candida glabrata that were resistance to fluconazole.Fluconazole resistance gene overexpression can be induced by fluconazole activation via signal transduction.

关 键 词：白色假丝酵母菌 光滑假丝酵母菌 氟康唑 耐药 

分 类 号：R965[医药卫生—药理学]