3种青蒿素衍生物对日本血吸虫吡喹酮抗性株童虫的体内作用效果观察

In-vivo efficacy of three artesiminin derivatives against schistosomulum of praziquantel-resistant Schistosoma japonicum

目的：观察3种青蒿素衍生物双氢青蒿素、青蒿琥酯和蒿甲醚对日本血吸虫吡喹酮抗性株童虫的体内作用效果。方法以经11轮亚治疗剂量吡喹酮筛选的日本血吸虫为吡喹酮抗性株，以未暴露于吡喹酮的日本血吸虫作为吡喹酮敏感株，收集2虫株尾蚴感染小鼠，以300 mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚对感染后7-8 d童虫分别进行2次灌服用药（总剂量600 mg/kg），所有小鼠于感染后45 d解剖，收集小鼠体内成虫并计数，计算减虫率和减雌率。结果300 mg/kg双氢青蒿素、蒿甲醚和青蒿琥酯2日疗法（总剂量600 mg/kg）对日本血吸虫吡喹酮敏感株7-8 d童虫的减虫率为69.8%-71.0%，减雌率为75.4%-79.8%；对日本血吸虫吡喹酮抗性株7-8 d童虫的减虫率为64.6%-66.1%，减雌率为69.3%-71.1%，差异均无统计学意义（均P〉0.05）。结论日本血吸虫吡喹酮抗性株对青蒿素类衍生物双氢青蒿素、青蒿琥酯和蒿甲醚依然敏感，青蒿素衍生物与吡喹酮在日本血吸虫中不存在交叉抗药性。

Objective To evaluate the in-vivo efficacy of three artemisinin derivatives artemether, artesunate and dihydroartemisinin against schistosomulum of praziquantel-resistant Schistosoma japonicum,. Methods The S. japonicum subjected to subcurative dose of praziquantel for 11 rounds was served as a praziquantel-resistant strain, while the field-derived strain without exposure to praziquantel was served as a praziquantel-susceptible strain. The mice infected with the two strains of cercaria were treated with artemether, artesunate and dihydroartemisinin at a single dose of 300 mg/kg by gavage in days 7 and 8 post-infection, respectively. All mice were dissected 45 days post-infection, and the adult worms were collected to estimate worm and female worm burden reductions caused by drug treatment. Results Administration of artemether, artesunate and dihydroartemisinin at a single dose of 300 mg/kg given on days 7 and 8 post-infection achieved total worm burden reductions of 69.8%-71.0%and female worm burden reductions of 75.4%-79.8%in mice infected with praziquantel-susceptible strain, whereas the same treatments reduced total worm burdens of 64.6%-66.1% and female worm burdens of 69.3%-71.1% in mice infected with praziquantel-resistant strain. There were no significant differences between the two strains. Conclusion Praziquantel-resistant S. japonicum remains sensitive to the three major artemisinin derivatives artemether, artesunate and dihydroartemisinin, and no cross-resistance is observed between praziquantel and artemisinin in S. japonicum.