土槿皮乙酸与抗真菌药联用对热带念珠菌活性的影响研究  

Synergistic Effect of Pseudolaric Acid B with Antifungal Drugs Against C.tropicalis

作　　者：王梓赫 路金明 王莹莹[1] 刁晗 孙德祥 王君[1] WANG Zi-he;LU Jin-ming;WANG Ying-ying;DIAO Han;SUN De-xiang;WANG Jun(The Affiliated Hospital of Qingdao University,Department of Dermatology,Qingdao,Shandong,266555,China)

机构地区：[1]青岛大学附属医院皮肤科,山东青岛266555

出　　处：《现代生物医学进展》2025年第2期231-239,共9页Progress in Modern Biomedicine

摘　　要：目的:研究土槿皮乙酸(PAB,Pseudolaric Acid B)与四种抗真菌药物(氟康唑、伏立康唑、卡泊芬净、两性霉素B)单药及联合应用对热带念珠菌的抗真菌活性。方法:采用体外肉汤微量液基稀释法测定PAB与四种抗真菌药单独应用及联合应用于对临床分离的11株热带念珠菌的最低抑菌浓度(MIC),并通过计算最低抑菌浓度值(FICI)判断两药联合抑菌效应。进一步应用时间-杀菌曲线动态监测PAB单药不同浓度及呈协同作用的用药组合的体外抑菌效果。结果:PAB单药对本实验纳入的11株临床分离热带念珠菌均具有良好抑菌效果,MIC值范围为4~8μg/mL,MBC值为8μg/mL。PAB与4种抗真菌药物联用对热带念珠菌的抗菌活性存在差异,PAB与伏立康唑联合作用于11株(100%)对伏立康唑敏感菌株均呈协同抑菌作用,其FICI范围为0.1875~0.5,与单独用药相比,MIC值降低了2~8倍。动态监测PAB与伏立康唑联合作用于热带念珠菌ATCC01463的时间-杀菌曲线,在48 h时联用组(伏立康唑+PAB)的OD值比单独使用伏立康唑组降低了2倍以上,进一步验证了伏立康唑与PAB联用对热带念珠菌具有协同抗菌作用;11株对氟康唑敏感菌株中,PAB与氟康唑联用对4株(36.3%)呈协同作用,余7株(63.6%)均呈无关作用,其FICI范围为0.375~0.75;两性霉素B与PAB联用对11株(100%)热带念珠菌的作用方式均表现为无关作用,FICI范围为1~2;8株对卡泊芬净敏感菌株中,卡泊芬净与PAB联用均表现为无关作用,3株对卡泊芬净耐药菌株中,仅有1株表现为协同作用,其FICI值为0.5,余耐药菌株均表现为无关作用。结论:PAB单药作用于热带念珠菌不仅有良好的抑菌活性,且表现出良好的杀菌作用。PAB与伏立康唑联用对热带念珠菌敏感株有较好的协同抑制作用。Objective:Investigate the antifungal activity of Pseudolaric Acid B(PAB)against Candi da tropicalis as a single agent and in combination with four kind of antifungal drugs(fluconazole,voriconazole,caspo fungin,amphotericin B).Methods:The minimum inhibitory concentration(MIC)of PAB alone and in combination with the four antifungal drugs against 11 clinically isolated strains of Candida tropicalis was determined by the microbroth dilution method in vitro,and the combined inhibitory effect of the two drugs was judged by calculating the fractional inhibitory concentration index(FICI).Further more,we used the time-skill curve to dynamically monitor the in vitro antibacterial effects of PAB alone at different concentrations,and drug combinations with synergistic effects.Results:PAB exhibited good inhibitory effects on all 11 clinical isolates of Candida tropicalis included in this experiment,with the MIC values ranging from 4 to 8μg/mL and the MBC value being 8μg/mL.The antibacterial activities of the combination of PAB and the four antifungal drugs against Candida tropicalis were different.When PAB was combined with VRC,all 11(100%)of the voriconazole-sensitive strains showed a synergistic inhibitory effect,with the FICI ranging from 0.1875 to 0.5.Compared with that in the monotherapy group,the MIC values reduced by 2-8 times.The time-kill curve of the combined action of PAB and VRC on Candida tropicalis ATCC01463 at 48 h showed that the OD value of the combined group(VRC+PAB)reduced by more than twice compared with that in the VRC group alone,which further indicated that the combination of VRC and PAB has a synergistic antibacterial effect on Candida tropicalis.Among the 11 fluconazole-sensitive strains,the combination of PAB and fluconazole showed synergistic effects towards 4 strains(36.3%)and irrelevanceeffect on the remaining 7 strains(63.6%),with the FICI ranging from 0.375 to 0.75.The combination of amphotericin B and PAB showed irrelevance effect on the 11(100%)Candida tropicalis strains,with the FICI rangin

关 键 词：土槿皮乙酸 热带念珠菌 体外药物敏感性实验 

分 类 号：R3[医药卫生—基础医学] R756.5