汉防己甲素对氟康唑抗白念珠菌菌丝相活性的增效作用及其机制研究  

In vitro study on the synergistic effect and mechanism of tetrandrine to fluconazole against hyphal form of Candida albicans

作　　者：李丰霞[1,2] 张宏[2] 单孔荣[1] 

机构地区：[1]广东药学院附属第一医院皮肤科,广州510080 [2]暨南大学附属第一医院皮肤科,广州510623

出　　处：《中国人兽共患病学报》2009年第1期13-16,共4页Chinese Journal of Zoonoses

基　　金：广东省科技计划项目(No.2004B33101004)

摘　　要：目的探讨体外汉防己甲素对氟康唑抗白念珠菌菌丝相活性是否有增效作用及其机制。方法参照微量稀释法确定汉防己甲素对白念珠菌菌丝相的非细胞毒性剂量,并测定氟康唑单独及联合汉防己甲素时对16株同一亲本白念珠菌菌丝相的MIC。荧光分光光度计测定加入及未加入汉防己甲素时此系细胞内罗丹明123的荧光强度。结果在终质量浓度≤2μg/mL汉防己甲素的作用下,白念珠菌菌丝相的存活率>95%;氟康唑单独作用时,对16株白念珠菌菌丝相的MIC值为0.250～64μg/mL;与汉防己甲素(2μg/mL)联合时,氟康唑对受试菌的MIC值降至0.125～8μg/mL,且终点清晰,"拖尾现象"消失。蓄积实验后,加入与未加入汉防己甲素的此系细胞内罗丹明123荧光强度分别为2.499～50.428、2.849～26.035(P=0.025);外排实验后,该值分别为1.006～7.267、0.191～6.685(P=0.000)。结论汉防己甲素在体外对氟康唑抗白念珠菌菌丝相活性有增效作用;汉防己甲素可抑制白念珠菌菌丝相药物外排泵的功能。To investigate the synergistic effect and mechanism of tetrandrine and fluconazole on the growth of the hyphal form of Candida albicans in vitro, the minimum concentration at which tetrandrine had no cytotoxic effect on the hyphal form of C. albincans was determind by microdilution test. The minimum inhibitory concentration（MIC） of fluconazole alone and in combination with tetrandrine against the hyphal form of 16 C. albicans was determined by CLSI M27-A microdilution method. and fluorescence Rh123 in the cells were determined by fluorimeter. When the concentration of tetrandrine was ≤2μg/mL, the survival rate of the hyphal form of C. albicans was more than 95%. The MICs of fluconazole alone to the above strains were 0. 250-64μg/mL, while those of fluconazole in combination with tetrandrine （2μg/mL） were 0. 125-8 μg/mL, with disappearence of the so-called ＂trailing＂ phenomenon. After accumulate test, with or without retrandrine, fluorescence Rh123 in the hyphal form of 16 C. albicans was 2. 499-50. 428 or 2. 849-26. 035. After efflux test, those were 1. 006-7. 267 or 0. 191- 6. 685（P=0. 000）. It is concluded that tetrandrine acts synergistically with fluconazole in the activity against the hyphal form of C. albicans in vitro, and it can suppress drug-efflux-transporter activity of C. albicans.

关 键 词：氟康唑 粉防己碱 白念珠菌 增效剂 

分 类 号：R379.4[医药卫生—病原生物学]