Abstract: Objective　To investigate the sensitivity of adult worms of filial generations from praziquantel⁃resistant and ⁃sensitive Schistosoma japonicum mixed infections to praziquantel. Methods　Mice were infected with the cercariae of an; experimentally generated praziquantel⁃resistant S. japonicum isolate [median effective dose (ED50) = 277.4 mg/kg] and a laboratory⁃maintained praziquantel⁃sensitive S. japonicum isolate (ED50 = 99.6 mg/kg) at a mixture ratio of 1∶1 and 2∶1, which was maintained in the laboratory via the mouse⁃snail cycle for 8 generations. Then, mice were infected with the cercariae of the 8th filial⁃generation parasite, and grouped 35 days post⁃infection. Mice in the 5 treatment groups were given praziquantel treatment by gavage at a single oral dose of 37.5, 75, 150, 300 mg/kg and 600 mg/kg, while animals in the control group was administered orally with 2.5% cremophor EL. All mice were sacrificed 14 days post⁃treatment and adult worms were collected by perfusion of the portal vein. The worm burden reductions and praziquantel ED50 values were calculated. The praziquantel⁃resistant S. japonicum isolate generated from experimental induction with 12 rounds of praziquantel treatment with sub⁃curative doses was maintained in the laboratory via the mouse⁃snail cycle, and mice were infected with the cercariae of the 8th filial⁃generation parasite. The praziquantel ED50 value against the 8th filial⁃generation adults was measured. Results　After mice were infected with the mixture of cercariae of PZQ⁃resistant and ⁃sensitive S. japonicum isolates at a ratio of 1∶1, the praziquantel ED50 was 135.2 mg/kg against the adults of the 8th filial⁃generation parasite. After mice were infected with the mixture of cercariae of PZQ⁃resistant and ⁃sensitive S. japonicum isolates at a ratio of 2∶1, the praziquantel ED50 was 129.2 mg/kg against the adults of the 8th filial⁃generation parasite. In addition, the praziquantel ED50 was 208.4 mg/kg against the adults of the 8th filial⁃generation S. japonicum without the selection pressure of praziquantel. Conclusions　Compared with the experimentally induced praziquantel⁃resistant S. japonicum isolate, the adult worms of the filial⁃generation S. japonicum show a reduced sensitivity to praziquantel in the same host following infection with the mixture of cercariae of praziquantel⁃resistant and ⁃sensitive S. japonicum isolates. The adult worms of the filial generation of the praziquantel⁃resistant S. japonicum isolate without the selection pressure of praziquantel may still maintain the resistance to praziquantel.

Key words: Schistosoma japonicum, Praziquantel, Drug resistance, Median effective dose (ED50)

摘要： 目的　测定实验诱导产生的日本血吸虫吡喹酮抗性株与实验室保种传代的日本血吸虫吡喹酮敏感株混合感染后产生的子代成虫对吡喹酮的敏感性。方法　取实验室诱导产生的日本血吸虫吡喹酮抗性株[吡喹酮半数有效剂量（ED50值）为277.4 mg/kg]尾蚴与实验室传代保种的日本血吸虫吡喹酮敏感株（吡喹酮ED50值为99.6 mg/kg）尾蚴，分别按1∶1和2∶1混合后感染小鼠。后在实验室经小鼠⁃钉螺循环8代后，取尾蚴感染小鼠。感染35 d后将小鼠分为对照组及5个给药组。5个给药组分别按37.5、75、150、300 mg/kg和600 mg/kg剂量一次性灌胃给予吡喹酮,对照组给予2.5%聚氧乙烯蓖麻油。给药14 d后解剖鼠并以静脉灌注法收集成虫，计算减虫率及吡喹酮对虫株的ED50值。取经12轮亚治疗剂量吡喹酮诱导筛选的日本血吸虫吡喹酮抗性株，置实验室经小鼠⁃钉螺循环常规传代，取子8代日本血吸虫尾蚴感染实验鼠，测定吡喹酮对此子代成虫的ED50值。结果　日本血吸虫吡喹酮抗性株与敏感株尾蚴按1∶1混合感染小鼠后，吡喹酮对子8代成虫ED50值为135.2 mg/kg；日本血吸虫吡喹酮抗性株与敏感株尾蚴按2∶1混合感染小鼠后，吡喹酮对子8代成虫ED50值为129.2 mg/kg；日本血吸虫吡喹酮抗性株未予吡喹酮压力传代，吡喹酮对子8代后成虫ED50值为208.4 mg/kg。 结论　与实验室诱导的抗性株相比，日本血吸虫吡喹酮抗性株与敏感株尾蚴混合感染同一宿主后所获的子代成虫对吡喹酮抗性有所降低。日本血吸虫吡喹酮抗性株不经药物压力传代，其子代成虫仍可能够维持对吡喹酮的抗性。

关键词: 日本血吸虫, 吡喹酮, 抗药性, 半数有效剂量（ED50）