卷柏素对唑类药物体外抗念株菌的增效作用  

Synergistic Effect of Selaginellin in Vitro on Azoles against Candidasis

作　　者：曹园 姚毅 刘维达[2] 沈永年[2] 郑海林 CAO Yuan;YAO Yi;LIU Wei-da;SHEN Yong-nian;ZHENG Hai-lin(Department of Pharmacy,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210036,China;Department of Mycology,Institute of Dermatology,Chinese Academy of Medical Sciences,Nanjing 210042,China)

机构地区：[1]南京中医药大学附属医院药学部,南京210036 [2]中国医学科学院皮肤病研究所真菌科,南京210042

出　　处：《天然产物研究与开发》2018年第9期1596-1600,共5页Natural Product Research and Development

基　　金：国家自然科学基金(81102772);国家科技重大专项(2009X09308-04)

摘　　要：本文研究中药卷柏中炔多酚类成分卷柏素与氟康唑、酮康唑联用对念珠菌的体外抗真菌效果,并初步探讨对氟康唑增效的分子机制。采用棋盘法测定两类药物联用对念珠菌体外抗真菌活性,以FICI法评价结果。实验结果表明,卷柏素与氟康唑、酮康唑合用对白念珠菌、近平滑念珠菌表现协同作用(FICI≤0. 5);对克柔念珠菌表现无关作用(FICI=1)。qRT-PCR检测卷柏素与氟康唑联用对白念株菌相关基因表达的影响显示,卷柏素能显著地逆转氟康唑诱导白念珠菌ERG5、ERG11、CDR1、CDR2、MDR1、FLU1和SIR2表达上调。Western-blot检测结果亦表明,卷柏素逆转组蛋白去乙酰化酶Sir2的上调。卷柏素显示出对氟康唑、酮康唑的抗念珠菌活性的体外增效作用。This study aimed to investigate the synergistic effect of selaginellin on azoles against Candidasis and to explore the related mechanism.Checkerboard microdilution method was used to study the antifungal activities of selaginellin in combination with fluconazole(FLC)or ketoconazole(KEC)against Candidasis.Fractional inhibitory concentration index(FICI)was employed as the interpretation standard.Synergistic effects were showed by SEL in combination with FLC and KEC against Candida albicans,C.parapsilosis with FICI of 0.5.However,no synergy was found for SEL and FLC or KEC against C.kruser.mRNA expressions of related genes in C.albicans were assayed by quantitative real time PCR(qRT-PCR).SEL exhibited reversal effect on the upregulated expressions of ERG5,ERG11,CDR1,CDR2,MDR1,FLU1,SIR2 by 86%,71%,62%,67%,56%,36%and 52%induced by FCL in C.albicans.Furthermore,the expression of Sir2 was detected by Western-blot,and likewise,SEL displayed reversal effect on the upregulated expressions of Sir2 induced by FCL.These results indicated that SEL had the in vitro effect to enhance the activities of FLC and KEC against C.albicans and C.parapsilosis.

关 键 词：卷柏素 氟康唑 酮康唑 念珠菌 增效作用 棋盘法 

分 类 号：R285.5[医药卫生—中药学]