抗真菌药对复发急性弓形虫病小鼠的保护研究

Antifungal therapy for the relapse of acute toxoplasmosis in mice

目的了解氟康唑或伊曲康唑对复发急性弓形虫病小鼠的保护作用。方法将感染弓形虫Prugniaud株(PRU株)2月后的ICR小鼠按以下方法进行分组:环磷酰胺组(CTX),环磷酰胺+氟康唑组(CTX+F),环磷酰胺+伊曲康唑组(CTX+I),环磷酰胺+阿奇霉素组(CTX+A),阿奇霉素浓度为250mg/kg·d,氟康唑和伊曲康唑组根据浓度不同又分为20mg/kg·d、30mg/kg·d和40mg/kg·d 3个组,同时设置正常小鼠+环磷酰胺(N+CTX)和感染组(In)对照。除In组外,其余各组每天腹腔注射环磷酰胺(100mg/kg·d),同时CTX+F、CTX+I和CTX+A组小鼠用灌胃方法分别喂食不同浓度的氟康唑、伊曲康唑和阿奇霉素,连续用药14d。结果实验结束时,CTX组小鼠全部死亡,CTX+A组、N+CTX组及In组小鼠全部存活,CTX+A组与CTX组存活率有显著差异(P=0.016)。CTX组、F组、I组和A组对复发急性弓形虫病小鼠的存活情况差异及其显著(P=0.000);阿奇霉素效果好于氟康唑(P=0.001),而氟康唑作用强于伊曲康唑(P=0.000)。但是氟康唑或伊曲康唑组由于药物剂量不同所导致的存活率无显著差异。CTX组与In组、F组、I组和A组比较,小鼠脑组织包囊数量明显增加(P=0.001),但是A组、I组、F组和In组之间的包囊数差别及F组和I组各个浓度之间包囊数的差别均无统计学差异。结论氟康唑对复发急性弓形虫病小鼠能起到一定保护作用,其可作为临床上免疫低下患者同时并发弓形虫及其他机会性真菌感染时的备选药物。

To investigate the protective effect of fluconazole and itraconazole for the reactivated toxoplasmosis in mice, ICR mice infected with Toxoplasrna gondii （T. gondii）for two months were grouped as follows： cyclophosphamide（CTX） treatment; cyclophosphamide combined with fluconazole （CTX--F）, cyclophosphamide with itraconazole（CTX-FI）, and cyclo- phosphamide with azithromycin （CTX＋A）. Normal mice only given with CTX and mice with T. gondii infection were set up as control. The CTX doses mouse got was 100 mg/kg ~ d by intraperitoneal injection except the infection （In） group. At the same time, mice from CTX ~ F and CTX--I were administrated fluconazole or itraconazole at various concentrations of 20 mg/kg ~ d, 30 rng/kg ~ d and 40 mg/kg ~ d, respectively, and the concentration of azithromycin got by mice from CTX--A group was 250 mg/kg ~ d. The medicines were administrated for continuous 14 days. At the end of the experiment, the mice from CTX group were dead; however, the mice from CTX--A group, CTX group and In group were survival, and the survival rate between CTX% A and CTX was significant deviation（P~ 0. 016）. Survival deviation of mice was very significant, which came from CTX group, CTX ＋F group, CTX＋I group, and CTX--A group （P^0.000）. Azithromycin was the best in the three drugs, among which fluconazole effect was better than itraconazole （P= 0. 000）. However, survival rate resulted in by different fluconazole or itraconazole dose was not significant deviation. Compared CTX group with others, the number of cysts in the brain were obvious increased （P--0. 001）, but the number of cysts was no statistical difference among CTX-FA, CTX-F I, CTX＋F, and In groups. Although there were different cysts in three concentrations of CTX^F and CTX--I groups, there was no statistically significant. Ifs suggested that fluconazole could make some protection for the reactivated acute toxoplasmo sis in mice, and it could be an alternative to T. gondii infected patients who were immunity suppression or with opportunisticfungal infection.