吡喹酮衍生物DW-3-15对日本血吸虫PZQ抗性虫体的生物学效应观察

发布时间：2018-03-02 16:10

本文选题：日本血吸虫　切入点：吡喹酮　出处：《中国人兽共患病学报》2015年09期 　论文类型：期刊论文

【摘要】：目的通过体外观察吡喹酮(PZQ)衍生物DW-3-15对日本血吸虫PZQ抗性虫体的生物学效应,探讨该衍生物作为抗日本血吸虫候选新药的潜在价值。方法单性日本血吸虫尾蚴(70±5条)感染小鼠,21d后,用PZQ的半数有效剂量(ED50,25.98mg/kg)对小鼠进行灌胃给药,每天一次,连续30d,停药21d后,再给予小鼠治疗剂量PZQ(200mg/kg),连续5d,停药2周后肝门静脉灌注收集虫体,置DMEM培养液中培养,分别加入不同浓度PZQ和DW-3-15,作用16h后换新鲜培养液,继续培养72h,每隔24h体视显微镜下观察、记录一次虫体活力和形态变化,评价诱导虫体对PZQ及DW-3-15的敏感性。结果 PZQ和DW-3-15体外作用于未诱导日本血吸虫成虫的临界致死浓度(作用虫体72h活力降低率达90%的最低浓度)分别为14μmol/L和45μmol/L;诱导虫体对PZQ的敏感性较未诱导虫体显著下降,是其临界致死浓度的8倍(112μmol/L),而诱导虫体对DW-3-15的敏感性与未诱导虫体相比没有明显差异,临界致死浓度仍为45μmol/L。结论经诱导的日本血吸虫PZQ抗性虫体对DW-3-15没有交叉抗性;提示DW-3-15抗日本血吸虫的靶点可能与PZQ不同,具有作为抗日本血吸虫候选新药的潜在价值,值得进一步研究。
[Abstract]:Objective to observe the biological effects of DW-3-15, a derivative of praziquantel, on PZQ resistant parasites of Schistosoma japonicum in vitro. To explore the potential value of this derivative as a candidate new drug against Schistosoma japonicum. Methods mice were infected with 70 卤5 cercariae of Schistosoma japonicum for 21 days. Mice were given intragastric administration of PZQ with ED5050 25.98 mg / kg once a day. For 30 days, after 21 days, the mice were given the dosage of PZQ 200 mg / kg for 5 days. After 2 weeks, the worms were perfused into the portal vein of liver and cultured in DMEM medium. The mice were treated with different concentrations of PZQ and DW-3-15 respectively. After 16 h of treatment, fresh culture medium was changed. After 72 hours of culture, the changes of body activity and morphology were recorded under stereoscopic microscope every 24 hours. Results the critical lethal concentration of PZQ and DW-3-15 on uninduced adult Schistosoma japonicum was 14 渭 mol/L and 45 渭 mol / L respectively (the lowest concentration of 72 h activity reduction rate of 90%) was 14 渭 mol/L and 45 渭 mol / L, respectively. The sensitivity of the insect to PZQ was significantly lower than that of the uninduced one. The sensitivity of induced body to DW-3-15 was not significantly different from that of uninduced body, and the critical lethal concentration was still 45 渭 mol / L. ConclusionThe induced PZQ resistant worm of Schistosoma japonicum had no cross resistance to DW-3-15. The results suggest that the target of DW-3-15 against Schistosoma japonicum may be different from that of PZQ, and it has the potential value as a new drug against Schistosoma japonicum, which is worthy of further study.
【作者单位】：苏州大学医学部病原生物学系;
【基金】：国家863项目(No.2012AA0203006)资助~~
【分类号】：R532.21

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