复发性外阴阴道假丝酵母菌病药物敏感性与耐药基因表达的相关性分析

目的:探讨复发性外阴阴道假丝酵母菌病(RVVC)患者的致病白假丝酵母菌对6种抗真菌药物(两性霉素B、制霉菌素、咪康唑、益康唑、伊曲康唑、氟康唑)敏感性与耐药基因MDR1、CDR1、CDR2和PDR1表达水平的关系。方法:菌株取自昆明医科大学第一附属医院妇产科门诊外阴阴道假丝酵母菌病患者,经菌种鉴定取白假丝酵母菌213株(RVVC 76株,VVC 137株)后做体外药敏试验;荧光定量PCR对已确定敏感、中敏或耐药的菌株进行耐药基因表达检测。结果:PDR1基因仅在部分菌株中有表达,RVVC组的PDR1基因表达率明显低于VVC组(P<0.05);两性霉素B的VVC-耐药组高于VVC-中敏组(P<0.05),伊曲康唑的RVVC-耐药组高于VVC-敏感组、VVC-耐药组和RVVC-敏感组(P<0.05),即对两性霉素B耐药的VVC菌株、对伊曲康唑耐药的RVVC菌株PDR1表达均升高;CDR1、CDR2、MDR1在所有白假丝酵母菌中均有表达,仅CDR1基因表达量存在差异咪康唑VVC-中敏+耐药组高于VVC-敏感组(P<0.05),氟康唑VVC-中敏组表达高于VVC-敏感组和VVC-耐药组(P<0.05),即对咪康唑耐药的VVC菌株表达高于其敏感菌株,对氟康唑中敏菌株表达高于其敏感和耐药组。结论:RVVC的治疗可优选制霉菌素。致RVVC菌株对伊曲康唑明显耐药,且与PDR1基因高表达有关。致VVC菌株对咪康唑、氟康唑产生耐药可能与CDR1高表达有关。PDR1和CDR1可能同时参与RVVC的耐药机制,而与CDR2和MDR1关系不大。

Correlation between drug susceptibility and drug resistance gene expression in recurrent vulvovaginal candidiasis

Objective:To investigate the relationship between the sensitivity of Candida albicans to six antifungal drugs(amphotericin B,nystatin,miconazole,Econazole,itraconazole,fluconazole)and the expression levels of MDR1,CDR1,CDR2 and PDR1 in patients with recurrent vulvovaginal candidiasis(RVVC).Methods:213 strains of Candida albicans(RVVC 76,VVC 137)were isolated from patients with vulvovaginal candidiasis in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Kunming Medical University.The drug sensitivity test in vitro was carried out.The expressions of drug resistance genes of the strains which were confirmed to be sensitive,moderately sensitive or resistant was detected by fluorescent quantitative PCR.Result:The expression rate of PDR1 gene in RVVC group was significantly lower than that in VVC group(P<0.05).The expression rate of PDR1 gene in VVC resistant group was higher than that in VVC moderately sensitive group(P<0.05),and the expression rate of PDR1 gene in RVVC resistant group was higher than that in VVC sensitive group,VVC resistant group and RVVC sensitive group(P<0.05).CDR1,CDR2,MDR1 were expressed in all Candida albicans,only CDR1 gene expression was different:the expression of miconazole VVC medium sensitive+drug resistant group was higher than VVC sensitive group(P<0.05),and the expression of fluconazole VVC medium sensitive group was higher than VVC sensitive group and VVC drug-resistant group(P<0.05),the expression of VVC strains resistant to miconazole was higher than that of sensitive strains,and the expression of medium sensitive strains to fluconazole was higher than that of sensitive and drug-resistant groups.Conclusion:Nystatin is the best choice for the treatment of RVVC.The resistance of RVVC strains to itraconazole is related to the high expression of PDR1 gene.The resistance of RVVC strains to miconazole and fluconazole may be related to the high expression of CDR1.PDR1 and CDR1 may participate in the resistance mechanism of RVVC at the same time,but not related to CDR2 and MDR1.