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  

Biological effects of DW-3-15 against praziquantel-resistant Schistosoma japonicum

作　　者：赵波[1] 关志勋 段中良 许静[1] 曹蕴[1] 林彩[1] 王言言[1] 夏超明[1] 

机构地区：[1]苏州大学医学部病原生物学系,苏州215123

出　　处：《中国人兽共患病学报》2015年第9期789-794,799,共7页Chinese Journal of Zoonoses

基　　金：国家863项目(No.2012AA0203006)资助~~

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。Resistance to praziquantel （PZQ） for S. japonicum was induced to evaluate whether there is cross resistance to the PZQ derivative DW-3-15 for PZQ-resistant adult worms of S. japonicum. The mice infected with S. japonicum were given subcurative （effective dose required to kill 50~ of the worms, EDs0） PZQ orally on the 21st day after infection, for 30 consec- utive days. Then with 21 days interval mice were treated again with curative （200 mg/kg） PZQ for 5 successive days. Two weeks post-treatment, in vitro, we observed that the critical lethal concentration （the lowest dose required to make 72 h vitality reduction reach to 90~/0） of PZQ against adult worms induced was eight times as high as uninducible worms, while the critical lethal concentration of DW-3-15 against PZQ-resistant adult worms was the same as that of the uninducible. The data revealed that PZQ-resistant adult worms showed no cross resistance to DW-3-15. These results indicate that the targets of PZQ and DW-3-15 against S. japonicum may be different. DW-3-15 will perhaps be a potentially novel drug for treatment of schistoso- miasis.

关 键 词：日本血吸虫 吡喹酮 DW-3-15 交叉抗性 

分 类 号：R383.2[医药卫生—医学寄生虫学]