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作 者:兰栋 曾庆仁[1] 马璇 顾孔珍[1] 吴尚辉[1,3] LAN Dong;ZENG Qingren;MA Xuan;GU Kongzhen;WU Shanghui(Department of Parasitology,Xiangya School of Medicine,Central South University,Changsha,Hunan Province,410013;Yueyang Vocational Technical College,Yueyang,Hunan Province,414000;Department of Cell Biology,Center for Advanced Research,Central South University,Changsha,Hunan Province,410078,China)
机构地区:[1]中南大学湘雅医学院寄生虫系与细胞生物学中心,长沙410013 [2]岳阳职业技术学院,湖南岳阳414000 [3]中南大学高等研究中心细胞生物学研究室,长沙410078
出 处:《第三军医大学学报》2020年第13期1286-1291,共6页Journal of Third Military Medical University
基 金:湖南省教育厅科学研究项目(18C1764)。
摘 要:目的从抗其他病原感染的大环内酯类药物中筛选一种可杀日本血吸虫(Schistosoma japonicum,S.j)移行期童虫的制剂。方法选取克拉霉素(ClM)、阿奇霉素(AzM)和伊维菌素(IVM)在体外实验中设计3个不同剂量水平对S.j脱尾童虫作杀伤试验观察,以行为改变和染色差异作为判别虫体死与活的标志,以各药物组虫体死亡率大小来评价杀伤效果。取体外杀虫高效的IVM用于S.j感染小鼠后体内1~4 d虫体作治疗效果观察。结果在体外IVM 20μg/mL浓度条件下对S.j尾蚴脱尾童虫可致100%的杀伤率,且显著高于吡喹酮(PZQ)和青蒿琥酯(ARS)的杀伤效果(P<0.05)。IVM在0.4 mg/kg×2次的剂量对S.j感染小鼠后1~2 d的童虫杀死率为53.37%,与感染对照组比差异有统计学意义(P<0.01);对3~4 d的童虫杀死率为39.98%,与感染对照组相比差异有统计学意义(P<0.05)。用IVM与PZQ或ARS联合治疗,未出现增效或协同作用。结论大环内酯类药物中伊维菌素对体内外日本血吸虫移行期童虫有很好的杀伤效果。Objective To screen an effective drug which can kill migratory-stage schistosomula of Schistosoma japonicum(S.j)from macrocyclic drugs treating other pathogenic infections.Methods Firstly,3 doses of clarithromycin(ClM),azithromycin(AzM)and ivermectin(IVM)were used to kill the migratory-stage schistosomula in vitro.The behavior changes and difference in methylene blue staining were used as markers to distinguish the death or life of the worms.The mortality of each group was employed to evaluate the killing effects of different drug groups.IVM at the dose of highly killing effectiveness was used to treat the mice in 1 to 4 d after S.j infection in order to observe the therapeutic effect.Results IVM at a concentration of 20μg/mL showed 100%killing effect against early-stage schistosomula in vitro,which was significantly higher than that of praziquantel(PZQ)and artesunate(ARS)(P<0.05).When IVM was used to treat the mice at the dose of 0.4 mg/kg×2,the killing rate of S.j was 53.37%in 1~2 d(P<0.01)and 39.98%in 3~4 d(P<0.05)after infection,with statistical difference when compared with the control group.No synergistic or additive effect was observed when IVM was combined with PZQ or ARS.Conclusion Among macrocyclic drugs,IVM exerts good killing effect on migratory-stage schistosomula of S.j in vivo and in vitro.
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