重组人粒细胞巨噬细胞集落刺激因子与伊曲康唑联合对白念珠菌抗菌作用的实验研究

The Efficacy of rhGM-CSF in Combination with Itraconazole Against Candida albicans Infection

目的研究重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)与伊曲康唑联合抗白念珠菌的作用。方法体内实验:制备系统性白念珠菌感染小鼠模型,用不同剂量伊曲康唑单独或与rhGM-CSF联合应用于感染小鼠,观测其28d内的存活情况。体外实验:分离鼠外周血中性粒细胞及腹腔巨噬细胞,分别将其与不同浓度的伊曲康唑及伊曲康唑加rhGM-CSF与白念珠菌共同培养,通过计数菌落形成单位(cfu)来判定伊曲康唑单独或与rhGM-CSF联合应用的抗白念珠菌效果。结果伊曲康唑1.0mg/kg与rhGM-CSF25μg/kg联合应用能显著延长小鼠28d内的存活期,效果与单用伊曲康唑2.5mg/kg相等,而rhGM-CSF25μg/kg与伊曲康唑5mg/kg联合应用时效果相当于单用伊曲康唑10mg/kg。体外实验亦显示rhGM-CSF与伊曲康唑联用能减少白念珠菌数量。结论rhGM-CSF与伊曲康唑联合应用对抗小鼠系统性白念珠菌感染有较好的协同作用。

Objective To study the efficacy of recombinant human granulocye-macrophage colony-stimulating factor (rhGM-CSF) in combination with itraconazole against Candida albicans. Methods In vivo test, systemic Candida albicans infection murine model was established, and treated with rhGM-CSF alone or in combination with itraconazole. The survival rate of the mice was observed within 28 days. In vitro test, murine peripheral blood neutrophils and peritoneal macrophages were isolated and incubated with different concentrations of itraconazole or itraconazole plus rhGM-CSF in the presence of Candida albicans. Then the concentration of colony-forming units (cfu) was calculated to evaluate the efficacy of itraconazole used alone or in combination with rhGM-CSF. Results The survival time of mice within 28 days was significantly prolonged when rhGM-CSF (25 μg/kg) was used in combination with itraconazole (1.0 mg/kg), the effect was similar to itraconazole (2.5 mg/kg) used alone. Furthermore the effect of rhGM-CSF (25 μg/kg) in combination with itraconazole (5 mg/kg) was similar to that of itraconazole (10 mg/kg) used alone. In vitro, the concentration of cfu was also significantly decreased by the use of rhGM-CSF in combination with itraconazole. Conclusion The combination of rhGM-CSF and itraconazole shows a good synergistic effect against the murine systemic infection of Candida albicans.