汉防己甲素对氟康唑抗白念珠菌增效活性的分子机制探讨  

Molecular mecbanism of the synergy between tetrandrine and fluconazole against Candida albicans

作　　者：高爱莉[1] 张宏[1] 莫宏波[2] 姜红浩[1] 王凯丽[1] 巢和安[1] 

机构地区：[1]暨南大学附属第一医院皮肤科,广州510632 [2]暨南大学医学院

出　　处：《中华皮肤科杂志》2008年第2期97-100,共4页Chinese Journal of Dermatology

基　　金：广东省科技计划项目（NO2004833101004）

摘　　要：目的探讨汉防己甲素在体外对氟康唑增效作用的分子机制。方法分别提取16株白念珠菌酵母相总RNA，采用RT-PCR方法比较汉防己甲素作用前及作用24h后白念珠菌药物外排泵基因MDR1、FLU1、CDR1、CDR2在氟康唑敏感、剂量依赖性敏感、耐药株中的表达情况。结果在汉防己甲素作用前，MDR1、FLU1、CDR1、CDR2表达水平在氟康唑敏感、剂量依赖性敏感、耐药株间的差异均有统计学意义（P〈0．05）。汉防己甲素作用24h后，与作用前相比，MDR1在氟康唑耐药株中、FLU1在氟康唑剂量依赖性敏感、耐药株中、CDR1和CDR2在氟康唑敏感、剂量依赖性敏感、耐药株中表达水平的差异均有统计学意义（P〈0．05）。结论汉防己甲素在体外对氟康唑抗白念珠菌活性增效作用的分子机制与抑制药物外排泵基因MDR1、FLU1、CDR1、CDR2的表达均有关。Objective To investigate the molecular mechanism of the synergy between tetrandrine and fluconazole against Candida albicans. Methods The non-cytotoxic concentrations of tetrandrine, and the minimal inhibitory concentrations of fluoconazole alone and in combination with tetmndrine for C.albicans were determined in previous studies. A total of 16 strains of C.albicans were divided into three groups： fluconazole-susceptible group （n = 11 ）, dose-dependent fluconazole-susceptible group （n = 3 ） and fluconazole-resistant group （n = 2）. The C.albicans strains were cultured and treated with tetrandrine. RT-PCR was used to detect the expressions of efflux pump genes including MDR1, FLU1, CDR1 and CDR2 in these three groups of C.albicans before and after 24 hours of culture with or without the treatment of tetmndrine. Results Before the exposure to tetrandrine, the expressions of MDR1, FLU1, CDR1, CDR2 were significantly lower in fluconazole-susceptible C.albicans strains than in dose-dependent fluconazole-susceptible and fluconazole-resistant strains （F = 8.54, 11.16, 16.52, 14.61, all P 〈 0.05 ）. The 24-hour exposure to tetrandrine significantly decreased the expressions of MDR1 in fluconazole-resistant C.albicans strains, FLU1 in fluconazole-susceptible and fluconazole-resistant strains, and CDR1 as well as CDR2 in all the three groups of C.albicans strains （P 〈 0.05 or 0.01 ）. Conclusion The molecular mechanism for the synergy between tetrandrine and fluconazole against C. albicans in vitro may be related to the down-regulation of MDR1, FLU1, CDR1 and CDR2 expressions.

关 键 词：氟康唑 粉防己碱 念珠菌 白色 基因 MDR FLU1 CDR1 CDR2 

分 类 号：R285.5[医药卫生—中药学]