【摘要】 目的 基于蜡螟感染模型探究亚抑菌浓度(sub-MIC)氟康唑(fluconazole, FLU)对光滑念珠菌毒力的影响。方法收集青海省人民医院2021年4月至2022年10月临床分离非重复的光滑念珠菌作为实验菌株，采用ATB法测定FLU对光滑念珠菌的最低抑菌浓度(MIC)。采用蜡螟感染模型检测光滑念珠菌的毒力，并采用病理学和病原学方法评估建模是否成功。穿刺及不同sub-MIC FLU对健康蜡螟的影响：对照组不做任何处理，实验组分为三组，即PBS组(注射10μL PBS)、FLU亚组(分别注射10μL FLU药液，使感染蜡螟体内FLU浓度为0.5 mg/kg、1 mg/kg、2 mg/kg、4 mg/kg、8 mg/kg、16 mg/kg)和穿刺组(微量注射器穿刺但不注射)。不同sub-MIC的FLU对光滑念珠菌感染蜡螟的影响：采用2.50×10~6酵母/只剂量感染蜡螟，2 h后，对照组再注射10μL PBS,实验组再注射不同浓度FLU工作液，观测对光滑念珠菌感染的蜡螟的治疗效果。结果 FLU对9株临床分离的光滑念珠MIC为8～32 mg/L,光滑念珠菌ATCC2001的MIC为32 mg/L。实验组蜡螟肠组织病理切片中检测到酵母样孢子，肠组织培养出光滑念珠菌，对照组中肠组织病理切片和真菌培养均未发现真菌。穿刺可造成蜡螟损伤，但所致死亡率低于10%。1/2MIC FLU可提高光滑念珠菌感染蜡螟生存率，具有统计学意义(P<0.05),而1/4MIC、1/8MIC、1/16MIC FLU对光滑念珠菌感染蜡螟生存率较PBS无明显的干预作用，差异无统计学意义(P>0.05)。结论 1/2MIC FLU对光滑念珠菌感染的蜡螟具有一定的治疗作用，但浓度低于1/2MIC对感染蜡螟无明显的保护作用。更多还原

【Abstract】 Objective Based on the Galleria mellonella infection model, the effect of sub-MIC fluconazole on the virulence of Candida glabrata was investigated. Methods Non repetitive Candida glabrata strains clinically isolated from Qinghai Provincial People’s Hospital from April 2021 to October 2022 were collected, and the minimum inhibitory concentration(MIC) of fluconazole against Candida glabrata was determined by ATB method. The virulence of Candida glabrata was tested by the Galleria mellonella infection model, and the success of the model was evaluated by pathological and pathogenic methods. Effects of puncture and different sub-MIC FLUs on healthy Galleria mellonella: the control group did not do any treatment, and the experimental group was divided into three groups, namely PBS group(10 μL PBS), FLU subgroup(inject 10 μL fluconazole solution respectively, making the FLU concentration in the body of infected Galleria mellonella 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, and 16 mg/kg) and puncture group(micro syringe puncture but no injection). Use 2.50×10~6 yeasts/larva infected with Galleria mellonella, after 2 h, the control group was injected with 10 μL PBS, the experimental group was injected with different concentrations of FLU working solution, observing the therapeutic effect on the Galleria mellonellainfected by Candida glabrata.Results The MIC of fluconazole to 9clinically isolated Candida glabrata was 8mg/L～32mg/L,and that of Candida glabrata ATCC2001 was 32mg/L.Yeast-like spores were detected in the pathological section of the intestinal tissue of the Galleria mellonell in the experimental group,and Candida glabra was cultured in the intestinal tissue.No fungus was found in the pathological section and fungal culture of the intestinal tissue in the control group.Puncture could cause damage to the Galleria mellonella,but the mortality was less than 10%.1/2 MIC fluconazole could improve the survival rate of Candida glabratainfected Galleria mellonella with statistical significance(P<0.05),while 1/4 MIC,1/8 MIC,1/16 MIC fluconazole had no significant intervention effect on the survival rates of Candida glabratainfected Galleria mellonella compared with PBS and the difference was not statistically significant(P>0.05).Conclusion 1/2 MIC fluconazole had inhibitory effect on the virulence of Candida glabrata,but the concentration below 1/2 MIC had no obvious protective effect.更多还原