体外棋盘法分析粗糠柴苦素与氟康唑联合抗隐球菌作用

中国真菌学杂志　 2019, Vol. 14 　Issue (2): 90-94.

体外棋盘法分析粗糠柴苦素与氟康唑联合抗隐球菌作用

雷岩, 方伟, 张超, 廖万清

海军军医大学长征医院皮肤科, 全军真菌病重点实验室, 上海市医学真菌研究所, 上海市医学真菌分子生物学重点实验室, 上海 200003

收稿日期:2018-02-27 出版日期:2019-04-28 发布日期:2019-04-28
通讯作者: 张超,E-mail:zhangchao324@smmu.edu.cn;廖万清,E-mail:liaowanqing@smmu.edu.cn E-mail:zhangchao324@smmu.edu.cn;liaowanqing@smmu.edu.cn
作者简介:雷岩,男(汉族),硕士研究生在读.E-mail:leyan_119@smmu.edu.cn
基金资助:
上海市科委扬帆计划（17YF1425100）；上海市科委项目（16DZ0500401）；上海市医学真菌分子生物学重点实验室项目（17DZ2272900）资助

In vitro chessboard detection for anti-Cryptococcus effect of rattlerin and fluconazole

LEI Yan, FANG Wei, ZHANG Chao, LIAO Wan-qing

Department of Dermatology and Venereology, Changzheng Hospital, Naval military medical university, PLA Key Laboratory of Mycosis, Shanghai Institute of Medical Mycology, Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai 200003

Received:2018-02-27 Online:2019-04-28 Published:2019-04-28

摘要/Abstract

摘要：

目的应用棋盘法测定以及探究粗糠柴苦素在体外联合氟康唑抗隐球菌是否有增效作用。方法参照微量稀释法（M27-A3）对隐球菌进行氟康唑、粗糠柴苦素单药药敏实验[FLZ，RAT]，以及以分数抑菌浓度指数（FICI）为判定指标棋盘法联合药敏实验[FLZ，RAT]。结果粗糠柴苦素对37株隐球菌MIC值范围为32~256 μg/mL，在与氟康唑联合作用时，FICI均≤ 0.50，使氟康唑的MIC值降低了50%~93.75%。结论粗糠柴苦素对隐球菌具有一定的抗真菌作用，同时与氟康唑联合使用能够发挥协同作用，提高氟康唑对隐球菌的敏感性。

关键词: 粗糠柴苦素, 氟康唑, 隐球菌, 棋盘法, 联合药敏

Abstract:

Objective To determine whether there is synergistic effect of rattlerin combined with fluconazole against Cryptococcus in vitro by the checkerboard method. Methods According to the microdilution method (M27-A3), the fluconazole and rattlerin single drug susceptibility test[FLZ, RAT] and the Fractional Inhibitory Concentration Index (FICI) were used as the judgment indicators of combined drug susceptibility test[FLZ, RAT]. Results The MIC values of rattlerin to 37 strains of Cryptococcus were 32-256 μg/mL. When combined with fluconazole, FICI was ≤ 0.50, which reduced the MIC value of fluconazole by 2-16 times. Conclusion Rattlerin had a certain antifungal effect on Cryptococcus, and it could synergize with fluconazole to improve the sensitivity of fluconazole to Cryptococcus.

Key words: rattlerin, fluconazole, Cryptococcus, checkerboard method, combined drug sensitivity

中图分类号:

R379.5

雷岩, 方伟, 张超, 廖万清. 体外棋盘法分析粗糠柴苦素与氟康唑联合抗隐球菌作用[J]. 中国真菌学杂志, 2019, 14(2): 90-94.

LEI Yan, FANG Wei, ZHANG Chao, LIAO Wan-qing. In vitro chessboard detection for anti-Cryptococcus effect of rattlerin and fluconazole[J]. Chinese Journal of Mycology, 2019, 14(2): 90-94.

参考文献

[1] Zhang C, Chen M, Wang G, et al. Pd@Ag Nanosheets in combination with amphotericin B exert a potent anti-cryptococcal fungicidal effect[J]. Plos One, 2016, 11(6):1-18.
[2] 徐莉,黄几华,邹碧姬. 舍曲林联合两性霉素B抗不同基因型隐球菌的效果[J]. 热带医学杂志, 2018, 18(2):156-163.
[3] 代黎,姜远英,张大志. 抗真菌药物增效剂的研究进展[J]. 中国真菌学杂志, 2013, 8(2):116-119.
[4] 谭善伦,张大志,姜远英. 具有协同抗耐药真菌活性的天然小分子化合物研究进展[J]. 药学学报, 2014, 49(8):1097-1104.
[5] Pandey S, Chatterjee A, Jaiswal S, et al. Protein kinase C-delta inhibitor, rottlerin inhibits growth and survival of mycobacteria exclusively through shikimate kinase[J]. Biochem Biophys Res Commun, 2016, 478(2):721-726.
[6] Kulkarni RR, Tupe SG, Gample SP, et al. Antifungal dimeric chalcone derivative kamalachalcone E from Mallotus philippinensis[J]. Nat Prod Res, 2014, 28(4):245-250.
[7] Nyilasi I, Kocsubé S, Krizsán K, et al. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations[J]. Med Mycol, 2014, 52(2):140-148.
[8] 李强国,李听,曹存巍. 两种钙调磷酸酶抑制剂联合常用抗真菌药物对马尔尼菲青霉酵母相体外药敏的研究[J]. 广西医学大学学报, 2015, 32(2):169-172.
[9] 董怀怀,王元花,廖泽彬. 芒果苷协同氟康唑抗耐药白念珠菌作用研究[J]. 中国真菌学杂志, 2017, 12(2):78-85.
[10] 吴锐,刁文琦,宋延君. 以棋盘法测定汉防己甲素与伊曲康唑的体外联合抗烟曲霉作用[J]. 中国人兽共患病学报, 2013, 29(8):748-752.
[11] Joseph M, Spyros P, Emmanuel R, et al. Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo Simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus[J]. Antimicrob Agents Chemother, 2010, 54(2):602-609.
[12] 廖勇,杨苏腾,丛林. 格尔德霉素和环孢素联合常用抗真菌药对阿萨希毛孢子菌临床株体外药敏研究[J]. 实用皮肤病学杂志, 2018, 11(2):67-70.
[13] Deng S, Zhang C, Seyedmousavi S, et al. Comparison of the in vitro activities of newer triazoles and established antifungal agents against Trichophyton rubrum[J]. Antimicrob Agents Chemother, 2015, 59(7):4312-4314.
[14] Wei F, Zhenzong F, Wanqing L. Epidemiology of Cryptococcus and cryptococcosis in China[J]. Fungal Genet Biol, 2015, 78(2014), 7-15.
[15] 朱良华,李德东,王彦. 深部真菌感染治疗的新思路[J]. 第二军医大学学报, 2012, 33(5):558-561.
[16] 王彦,黄海,李健峰. 真菌耐药的研究进展[J]. 药学服务与研究, 2009, 9(3):166-170.
[17] 申玲,姜远英,曹永兵. 植物成分协同抗真菌作用的研究进展[J]. 中国真菌学杂志, 2013, 8(1):55-60
[18] 朱均昊,韩德忞,李莉. 华东地区新生隐球菌药物敏感性分析[J]. 检验医学, 2016, 31(9):761-764.
[19] Wang T, Liu C, Jia L. The roles of PKCs in regulating autophagy[J]. J Cancer Res Clin Oncol, 2018, 144(12):2303-2311.
[20] Lei L, Li Z, Zhong G. Rottlerin-mediated inhibition of chlamydia trachomatis growth and uptake of sphingolipids is independent of p38-regulated/activated protein kinase (PRAK)[J]. Plos one, 2012, 7(9):1-6.
[21] Song J, Zhou Y, Gong Y, et al. Rottlerin promotes autophagy and apoptosis in gastric cancer cell lines[J]. Mol Med Rep, 2018, 18(3):2905-2913.
[22] Maioli E, Daveri E, Maellaro E, et al. Non-conventional rottlerin anticancer properties[J]. Arch Biochem Biophys, 2018, 645(2018):50-53.
[23] Shivshankar P, Lei L, Wang J, et al. Rottlerin inhibits chlamydial intracellular growth and blocks chlamydial acquisition of sphingolipids from host cells[J]. Appl Environ Microbiol, 2008, 74(4):1243-1249.
[24] Woo SM, Lee WK, Min KJ, et al. Rottlerin induces cyclooxygenase-2 upregulation through an ATF4 and reactive oxygen species-independent pathway in HEI-OC1 cells[J]. Mol Med Rep, 2016, 14(1):845-850.