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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。
Objective To observe the toxic effects of auranofin, cisplatin, doxorubicin and 4N, H, B and O on the culture of Schistosoma japonicum in vitro and the inhibitory effect on the activity of thioredoxin glutathione reductase (TGR). Methods Adult Schistosoma japonicum was placed in RPMI 1640 medium. After cultured for 30-60 min, different concentrations of drugs were added and the activity, morphological changes and death of the parasites were observed at 6, 24, 48 and 72 h respectively. Subsequently, the drug-free fresh medium was used to observe the recovery of the viability of the parasites and calculate the LD50 of the drug. The activity of thioredoxin (TrxR) and glutathione reductase (GR) of Schistosoma japonicum TGR in drug-treated adult homogenate supernatant was measured. Results The lethal effects of 5μg / ml auranofin for 24 h, 20μg / ml 4N for 72 h, 60μg / ml H for 72 h and 80μg / ml cisplatin for 72 h were 100%, 60%, 66.7 %, 100%, LD50 values were 2.56,17.59,54.14μg / ml and 52.87μg / ml, other drugs had no effect on Schistosoma japonicum. The toxic effects of auranofin, 4N, cisplatin and H on adult worms were irreversible. Auranfen and cisplatin had an inhibitory effect on TGR activity of Schistosoma japonicum, while other drugs had no effect on TGR. 5 ~ 30μg / ml auranofin, 20 ~ 30μg / ml 4N, 70 ~ 150μg / ml cisplatin and 60 ~ 150μg / ml H for 24 h can make the morphology change. Conclusion The effects of auranofin, cisplatin, 4N and H compounds on the killing of Schistosoma japonicum in vitro were notable. The effects of auranofin and cisplatin on killing Schistosoma japonicum may be related to the inhibition of TGR activity.