血吸虫对吡喹酮抗药性的研究Ⅴ 吡喹酮对曼氏血吸虫吡喹酮抗性株和敏感株成虫皮层的损伤

STUDIES ON RESISTANCE OF SCHISTOSOMA TO PRAZIQUANTEL V.ADULT WORM TEGUMENTAL DAMAGE IN PRAZIQUANTEL-RESISTANT AND-SUSCEPTIBLE SCHISTOSOMA MANSONl TREATED IN VIVO

目的 体内比较吡喹酮对曼氏血吸虫吡喹酮抗性株与敏感株成虫皮层的损伤程度。方法 用各虫株尾蚴分别感染小鼠,感染后第57天,以300mg/kg微粒化吡喹酮悬液对小鼠作灌胃治疗;在灌药后10、30min和1、12、24h后剖杀感染小鼠,门静脉灌注收集成虫,按常规方法制成扫描电镜标本,扫描电镜下观察成虫体表的变化。结果 吡喹酮诱导的皮层损伤主要为虫体表形成泡状结构的薄壁隆起;给药10min,敏感株雄虫皮层可见较多小泡状物,而抗性株则少见;1h后,敏感株虫体表可见大量的泡状物,泡状物溃破可形成皮层损伤灶,抗性株仅见少量的泡状物;24h后,敏感株雄虫体表完全受损,部分皮层剥落,暴露出肌肉层,而抗性株仅见少量泡状物和破损的泡状物。给药1h后,敏感株雌虫开始出现少量泡状物,抗性株雌虫体表未见泡状损伤;12h后,敏感株雌虫泡状物数量增加,抗性株仅在有限区域见少量泡状物。结论 抗性株和敏感株成虫体表吡喹酮诱导的皮层损伤程度存在明显差异,敏感株的损伤程度重于抗性株,雄虫重于雌虫。

Objective To compare the effect of praziquantel on the tegument of adult Schistosoma mansoni worms between praziquantel-resistant and -susceptible parasite isolates in vivo. Methods Two isolates of S.mansoni, the 'gene-pooled' susceptible and the lab-selected resistant isolates were used to infect mice with cercariae respectively. On day 57 after infection, the mice were treated with a single sub-curative dose of micronized praziquantel (300 mg / kg) by oral gavages. At 10 and 30 mm and 1, 12, and 24 h after dosing, three mice from each groups infected with the two isolates were sacrificed and adult worms recovered by portal perfusion. Scanning electron microscopic observation on the tegument of Schistosoma adult worms in mice treated with praziquantel was performed. Results The damage induced by praziquantel to the tegument of S. mansoni consisted mainly of the formation of bleb-like structures protruding out from the surface. Ten minutes after dosing on the tegument of susceptible male worms numerous small spherical discrete blebs were present. Only a few blebs were found on the surface of male worms in the drug-resistant isolate. One hour after dosing, numerous blebs formed across the surface, and some blebs ruptured to form lesions on susceptible worms. A small number of blebs were observed on worms of the resistant isolate. After 24 hours the susceptible male worm tegument appeared to have been completely darn- aged and parts of the tegument been sloughed off revealing the muscle layer beneath. In contrast, only some disrupted were found on resistant worms. One hour after treatment, a small amount of blebs began to occur on limited areas of the surface of susceptible female worms, while no blebs was found on the surface of drug-resistant female worms. Twelve hours later, the damaged areas were enlarged and the number of blebs increased on susceptible female worms, while only a few blebs were found on a limited surface area of resistant female worms. Conclusion There were significant differences in the effect with praziquantel on the tegument of adult S. mansoni worms between praz-iquantel-resistant and -susceptible parasite isolates in vivo. More severe damage was inflicted by praziquantel on susceptible worms than that on praziquantel-resistant worms.