关键词: 蒿甲醚, 曼氏血吸虫, 剂量效应关系, 药物, 病理学

Abstract: 　Objective To investigate the effects of artemether on Schistosoma mansoni harboured in mice, with particular consideration on single dose-efficacy relationship, hepatic shift and artemether-induced alterations in worm morphology and histopathology. Methods Groups of mice, infected with 21d old S.mansoni, were treated with artemether at single oral doses of 12.5mg/kg to 600mg/kg. Worm burden reduction was assessed 28d post-treatment. The hepatic shift was investigated in mice infected with 46d old S. mansoni and treated with artemether at a single oral dose of 400 mg/kg within a period of 14d post-treatment. Morphological and histopathological observations were made in adult worms in mice, subject to single oral dose of artemether at 400mg/kg. Results The minimum effective dose of oral artemether against juvenile worms in mice was 200 mg/kg, resulting in a worm burden reduction of 81%. The hepatic shift commenced 8 h post-treatment, and all worms shifted to the liver 3-7d post-treatment. Fourteen days post-treatment, 31% of the worms returned to the mesenteric veins. Treatment with artemether resulted in decreased worm body size, expansion of the pharynx and dilation of the gut with marked reduction in pigment. Focal tegumental damage was observed among female worms with adherence of host leukocytes and degeneration of ovary and vitelline glands, as well as atrophy of testis in male worms. Artemether-damaged worms were surrounded and infiltrated by eosinophils. Conclusion The minimum effective dosage of artemether against 21d old S.mansoni in mice is 200mg/kg. Artemether also exhibits effect against adult schistosomes, including shrinkage and degeneration, and can lead to worm death. The predominant inflammatory cell surrounded and infiltrated into the artemether-damaged worm is eosinophil.

Key words: Artemether, Schistosoma mansoni, Dose-Response Relationship, Drug, Pathology