中文摘要：

目的观察金诺芬、顺铂、阿霉素及化合物4N、H、B、O对体外培养日本血吸虫的毒性作用,以及对硫氧还蛋白谷胱甘肽还原酶（TGR）活性的抑制作用。方法取日本血吸虫成虫置于RPMI 1640培养基中,培养30～60 min后,加入不同浓度药物,分别于6、24、48、72 h观察虫体活力、形态改变及死亡情况。随后换无药物的新鲜培养基,观察虫体活力的恢复情况,并计算药物半数致死剂量（LD50）。测定药物处理后的成虫匀浆上清液中日本血吸虫TGR的硫氧还蛋白原酶（TrxR）和谷胱苷肽还原酶（GR）的活性。结果 5μg/ml金诺芬作用24 h、20μg/ml 4N作用72 h、60μg/ml H作用72 h、80μg/ml顺铂作用72 h对日本血吸虫成虫致死率分别为100%、60%、66.7%、100%,LD50值分别为2.56、17.59、54.14μg/ml和52.87μg/ml,其他药物对日本血吸虫无作用。金诺芬、4N、顺铂、H对成虫的毒性作用具有不可逆性;金诺芬、顺铂对日本血吸虫的TGR酶活性有抑制作用,其他药物对TGR无作用。5～30μg/ml金诺芬、20～30μg/ml 4N、70～150μg/ml顺铂及60～150μg/ml H作用24 h均可使虫体形态发生改变。结论金诺芬、顺铂、化合物4N和H对体外培养的日本血吸虫成虫具有杀伤作用,其中金诺芬、顺铂杀伤日本血吸虫成虫的作用可能与其抑制TGR活性有关。

英文摘要：

Objective To observe the toxicity of auranofin,cisplatin,adriamycin,compounds 4N,H,B,O against Schistosoma japonicum adult worms in vitro and their inhibition on thioredoxin glutathione reductase（TGR）.Methods The drugs mentioned above with different concentrations were added into RPMI 1640 medium with Schistosoma japonicum adult worms,which had been cultured for 30-60 min.The activity,morphological changes and death situation of the worms were observed after 1,6,24,48 h and 72 h,respectively,then the worms were transferred to fresh medium without drugs to observe whether their activity would be recovered,and 50% lethal dose（LD50） of the drugs against adult worms was determined.The TrxR and GR activities of thioredoxin glutathione reductase of Schistosoma japonicum in homogenized supernatant of adult worms processed by drugs were tested following the DTNB reduction and NADPH oxidation methods.Results The mortality rates of 5 μg/ml of auranofin treating for 24 h,20 μg/ml of 4N treating for 72 h,60 μg/ml of H treating for 72 h,and 80 μg/ml of cisplatin treating for 72 h on adult worms were 100%,60%,66.7% and 100%,respectively,and there were statistically significant differences compared with the negative control group.LD50（s） of auranofin,4N,H and cisplatin were 2.56,17.59,54.14 μg/ml and 52.87 μg/ml,respectively,but no toxic effects of other drugs on schistosome worms were found.The toxic effects of auranofin,4N,cisplatin and H on adult worms were irreversible.Auranofin and cisplatin inhibited TGR activity of Schistosoma japonicum,but other drugs had no similar effect.5-30 μg/ml of auranofin,20-30 μg/ml of 4N,70-150 g/ml of cisplatin,and 60-220 μg/ml of H caused the morphological changes of the worms after treating for 24 h.Conclusions Auranofin,cisplatin and compounds 4N and H have toxicity on Schistosoma japonicum adult worms in vitro,and the schistosomicidal effect of auranofin and cisplatin may be related to the inhibition of TGR activity.