摘要
目的 观察青蒿琥酯对不同阶段日本血吸虫的损害作用,揭示青蒿琥酯的杀虫机制.方法小鼠感染尾蚴18 d时给予青蒿琥酯300 mg/kg,24 h后灌注法收集童虫,并用紫外吸收法和Bradford标准曲线法测定青蒿琥酯对日本血吸虫18 d童虫DNA和蛋白质含量的影响;分别将10条虫体在含有3H胸腺嘧啶核苷的培养基中培养24 h后,用滤膜法和匀浆法测定青蒿琥酯对标记核苷掺入童虫DNA的影响;感染血吸虫尾蚴21 d的小鼠一次性灌服青蒿琥酯300 mg/kg,给药后21 d,灌注法收集成虫,观察青蒿琥酯对日本血吸虫成虫生殖器官大小及生殖细胞发育的影响;小鼠感染血吸虫33 d时给予同样的青蒿琥酯进行治疗,24 h和48 h后处死小鼠,将肝脏制作组织切片,在光镜下观察同等剂量青蒿琥酯引起的成虫肝移和形态学变化的影响.结果 青蒿琥酯体内作用18 d的虫体,24 h后,童虫的DNA和蛋白质含量均较对照组明显减少,减少率分别为23.0%和33.6%（P＜0.01）;在含有3H胸腺嘧啶核苷的培养基中培养24 h后,童虫摄入标记的核苷及核苷掺入童虫DNA的量较对照组也明显减少,减少率分别为61.1%和40.8%（P＜0.01）;21 d给药组小鼠体内雌虫卵巢的成熟、发育受到了抑制;药物作用于虫体33 d后能明显引起虫体形态的变化,特别是虫体体表.结论 青蒿琥酯能减少日本血吸虫童虫蛋白质和DNA的含量,能明显抑制虫体对标记核苷的摄入以及标记核苷掺入虫体DNA的量,能引起虫体体表明显的组织形态学变化,并且能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵,能有效减轻血吸虫病的病情和控制传播.
Objective To investigate the details of the therapeutic effects of artesunate against Schistosoma japonicum infection in mice and examine the damage to different stages of S. japonicum. Methods Mice were treated with artesunate 300 mg/kg for 18 d after infection. Twenty-four hours after treatment,schistosomula were collected to determine DNA and protein contents using ultraviolet ray-absorption and Bradford method, respectively. Every 10 schistosomula were maintained in drug-free medium containing 3H thymidine for 24 h ,the tritiated nucleoside uptake and incorporation into nucleic acid were measured using filter membrane and homogenate. Mice infected were orally administered with artesunate at 21 d,the changes of the size of reproduction organ and the development of reproductive cell were investigated. Mice infected with S. japonicum were treated with the same dose of artesunate at 33 d,then the liver tissue sections were examined under a light microscope to investigate the hepatic shift and artesunate-induced alterations in worms. Results One dose of 300 mg/kg artesunate against 18 d schistosomula caused reduction of the DNA and protein contents decreased by 23.0% and 33.6% compared to the control group（P 〈 0.01）. When the above-mentioned schistosomula were in vitro exposed to the tritiated nucleoside for 24 h, apparent decrease in tritiated nucleoside uptake with reduction of 61. 1% （P 〈0. 01） was seen in the treated schistosomula. The incorporation of 3H thymidine into the schistosomula DNA 24 h after co-incubation was reduced by 40.8% （P 〈0.01）. The significant changes in reproductive system of adult parasites treated at 21 d after infection,suggested that artesunate inhibits sexual maturation. Light microscopic examination revealed that artesunate caused morphological damage to adult ones at 33 d,especially on the worm tegument. Conclusion Artesunate can mitigate the pathogenetic condition and control the spread of schistosomiasis japonicum by inhibiting nucleic acid and protein metabolism
出处
《国际医学寄生虫病杂志》
CAS
2010年第4期205-211,共7页
International JOurnal of Medical Parasitic Diseases
基金
江苏省自然科学基金（SBK2009076）
关键词
日本血吸虫
青蒿琥酯
生化代谢
性成熟
组织病理学
Schistosoma japonicum
Artesunate
Biochemical metabolism
Sexual maturation
Histopathology
