丹参酮分别联合伊曲康唑、特比萘芬对红色毛癣菌体外抗菌活性研究

Research on In Vitro Antimicrobial Activity of Tanshinone in Respectively Combined with Itraconazole and Terbinafine Against Trichophyton Rubrum

目的:探讨丹参酮分别联合伊曲康唑、特比萘芬对红色毛癣菌的体外抗菌活性。方法:选取临床分离的红色毛癣菌40株进行体外药物敏感试验,参照美国临床和实验室标准化研究所M38-A2方案测定丹参酮、伊曲康唑及特比萘芬的最低抑菌浓度(minimum inhibitory concentration,MIC),采用分级抑制浓度指数(factional inhibitory concentration index,FIC)评定联合用药效果,并观察不同浓度丹参酮对红色毛癣菌的作用。结果:丹参酮、伊曲康唑及特比萘芬对红色毛癣菌MIC的差异有统计学意义(P<0.05),其中伊曲康唑MIC较低,丹参酮MIC较高。丹参酮仅联合0.031 2、0.062 5μg/ml的伊曲康唑时,FIC<1所占比例分别为42.50%(17/40)、45.00%(18/40),以协同作用为主;而联合其他质量浓度的伊曲康唑时以拮抗作用为主,不同质量浓度组间比较的差异均有统计学意义(P<0.05)。丹参酮联合不同质量浓度的特比萘芬时均以拮抗作用为主,不同质量浓度组间比较的差异均有统计学意义(P<0.05)。丹参酮作用于红色毛癣菌可使菌丝萎缩,出现多处破损及断裂,细胞浆、细胞核破碎,形态不规则。结论:丹参酮分别联合伊曲康唑、特比萘芬对红色毛癣菌均以拮抗作用为主,故应避免联合应用。丹参酮可使红色毛癣菌超微结构发生明显改变,进而发挥有效抗真菌作用。

OBJECTIVE:To probe into the in vitro antimicrobial activity of tanshinone in respectively combined with itraconazole and terbinafine against trichophyton rubrum.METHODS:40 strains of trichophyton rubrum were isolated and selected for in vitro drug sensitivity test,the minimum inhibitory concentrations (MIC) of tanshinone,itraconazole and terbinafine were determined by reference to M38-A2 protocol of American Institute of Clinical and Laboratory Standardization,effects of combined drug application was evaluated by fractional inhibition concentration index (FIC),and the effects of different concentrations of tanshinone on trichophyton rubrum were observed.RESULTS:Difference in MIC among tanshinone,itraconazole and terbinafine against trichophyton rubrum was significantly significant ( P <0.05),of which the MIC of itraconazole was relatively lower and the tanshinone was higher.When tanshinone was combined with 0.031 2 μg/ml and 0.062 5 μg/ml of itraconazole,the proportions of FIC<1 were respectively 42.50%(17/40) and 45.00%(18/40),mainly were synergistic effects;while other concentrations of itraconazole were mainly antagonistic effects,and the differences among different concentrations were statistically significant ( P <0.05).Tanshinone combined with different concentrations of terbinafine were mainly antagonistic effects,and the differences among different concentrations were statistically significant ( P <0.05).Tanshinone can cause atrophy of mycelium by acting on trichophyton rubrumthe,with multiple damages and breakages,cytoplasm and nucleus breaks,irregular shapes.CONCLUSIONS:Tanshinone combined with itraconazole and terbinafine are mainly antagonistic to trichophyton rubrum,so that the combined application should be avoided.While tanshinone can significantly change the ultrastructure of trichophyton rubrum,and thus exert an effective antifungal effect.