rhM-CSF对化疗小鼠抗白念珠菌感染的实验研究

人巨噬细胞集落刺激因子（M-CSF）是一种能刺激巨噬细胞系细胞生长、增殖、分化的生长因子，其抗真菌活性越来越受到重视。利用小鼠化疗损伤模型研究家蚕表达的重组人巨噬细胞集落刺激因子（rhM-CSF）单独或与氟康唑联合应用时对白念珠菌感染的防治作用。一次性腹腔注射环磷酰胺200mg/kg，导致小鼠免疫功能下降。当小鼠外周血白细胞数降至最低时尾静脉注射白念珠菌。rhM-CSF治疗组分别采用每天10、50、250、500μg/kg4种剂量连续6d。氟康唑每天300μg/kg，连续5d。记录各组小鼠的死亡天数和只数，计算平均存活天数和存活率。结果：rhM-CSF及rhM-CSF和氟康唑联合治疗组的小鼠存活率较空白组显著提高。250μg/kgrhM-CSF和氟康唑联合治疗组效果最好，小鼠存活率由空白组的14.3％提高至50.0％，存活小鼠肾脏白念珠菌菌落数也明显降低。表明家蚕表达的rhM-CSF对化疗损伤小鼠白念菌感染有明显的防治作用。为临床免疫功能低下病人感染白念珠菌的治疗提供了一种有效的新药。

Antifungal Activity of Recombinant Human Macrophage Colony Stimulating Factor in Model of Candidiasis in Chemotherapeutically Treated Mice

M-CSF is a hematopoietic growth factor that stimulates the proliferaion and differentiation of mononuclear progenitors into mature cells and promotes the production of other cytokines. There are an increasing number of reports describing the in vitro or in vivo antifungal effect of M-CSF. The present study was designed to investigate the effect of rhM-CSF expressed in silkworm on chemotherapeutically treated mice with invasive fungal disease. 200 mg/kg cyclophosphamide (CY) was injected (ip) into mice to make the model of chemotherapeutically lesions. Four days after CY injection the mice were infected (iv) with C. albicans (2 x 104cells per mouse) and were administered differtdoses of rhM-CSF, alone in combination with fluconazole (300 ug/ kg), once a day for 6 days. The number of survival animals in each group was determined every day until the end of the 3-week experimental period. Survival rates and medial survival time were evaluated by SPSS. The results demonstrate that combination therapy with rhM-CSF and FLCZ showed higher survival rate more than in the therapy with either rhM-CSF or FLCZ alone. When 250 ug/kg rhM-CSF treatment was combined with FLCZ, the survival rate over a 3-week period reached 50.0% (cf. survival rates of 28.6% for FLCZ alone and 35.7% for hM-CSF alone) and median liter of C. albicans culture from the kidneys were greatly decreased relative to the control. These results indicate that rhM-CSF expressed in silkworm could effectively improve the survival rate and medial survival times of chemotherapeutically treated mice with invasive fungal disease.