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目的应用吡喹酮(PZQ)亚治疗剂量对感染小鼠体内日本血吸虫虫体进行药物压力下的耐药虫体筛选,并探讨经筛选后的虫体对PZQ的敏感性及其超微结构变化。方法应用日本血吸虫雄虫PZQ半数有效致死剂量(ED50)为亚治疗剂量,对感染6周后小鼠喂饲给药30d;肝门静脉灌注法收集雄性成虫体外培养,加入不同浓度PZQ连续培养5d,根据虫体活力,评价对PZQ的敏感性,同时用扫描电镜观察虫体超微结构的变化。结果经实验获得日本血吸虫雄虫PZQ的ED50为20.89mg/kg;应用该剂量对感染小鼠体内连续用药30d后,体外培养观察显示虫体对PZQ敏感性显著下降,扫描电镜观察表明皮层及抱雌沟损害较正常虫体明显减轻;筛选后虫体再用治疗剂量PZQ200mg/kg连续给药5d后,体外培养观察显示,虫体在不同浓度PZQ作用下存活率仍达100%,扫描电镜显示体表及抱雌沟损害比单纯用药30d的虫体更轻。结论在持续药物压力下,感染宿主体内的日本血吸虫可能对PZQ产生一定的耐受性。
OBJECTIVE To investigate the drug resistance of Schistosoma japonicum infected with PZQ in mice infected with PZQ and investigate the changes of the susceptibility to PZQ and the ultrastructure of the infected parasites . Methods The half dose of PZQ of Schistosoma japonicum was used as sub-therapeutic dose, and the mice were dosed for 6 weeks after infection for 30 days. Male adult cells were harvested in vitro by hepatic portal vein perfusion and cultured continuously for 5 days with different concentrations of PZQ. According to the vitality of the parasites, the sensitivity to PZQ was evaluated, and the ultrastructural changes of the parasites were observed with a scanning electron microscope. Results The ED50 of PZQ of Schistosoma japonicum was 20.89 mg / kg. After 30 days of administration, the sensitivity of PZQ to Schistosoma japonicum was significantly decreased. The results of scanning electron microscopy The results of in vitro culture showed that the survival rate of the parasites was still 100% under the different concentration of PZQ, and the results of scanning electron microscopy Body surface and hold the female ditch damage than simple medication 30d lighter. Conclusions Under the persistent drug pressure, Schistosoma japonicum infected in the host may have some tolerance to PZQ.