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目的评价5种地西泮类衍生物B3、B7、B8、B26、B30抗血吸虫效应并探讨其作用机制。方法取雄性日本血吸虫和曼氏血吸虫成虫(10条/皿)培养于DMEM培养液中,分别加入5种地西泮衍生物B3、B7、B8、B26、B30,工作浓度均为50 mol/mL,培养16h,在体视显微镜下观察药物洗涤后24h～72h的虫体存活状态,计算其存活率及活力降低率。以细胞肌松素D和钙通道阻滞剂预处理虫体1h后再加B3和B30共同培养16h,观察拮抗效应。结果在B3实验组中,日本血吸虫存活率和活力降低率为0%和100%,曼氏血吸虫为20%和93.3%,B30实验组中,日本血吸虫和曼氏血吸虫的存活率分别为0%和13%;两者的活力降低率则分别为100%和94.3%。B7、B8、B26实验组抗日本血吸虫效应不明显,但对曼氏血吸虫的作用略好于日本血吸虫。细胞肌松素D可显著拮抗B3、B30的抗日本血吸虫效应,拮抗后B3实验组虫体存活率和活力降低率分别为80%和59%～63%、B30实验组为70%和46%～55%,钙通道阻滞剂尼非地平、尼群地平拮抗B3、B30后虫体存活率为10%～40%,活力降低率为85%～96%。结论地西泮衍生物B3、B30在体外具有显著抗血吸虫效应(P<0.01),且日本血吸虫对该2种衍生物的敏感性好于曼氏血吸虫;而其余3种衍生物的抗曼氏血吸虫作用则更明显。细胞肌松素D对B3、B30具有显著的拮抗作用;钙通道阻滞剂尼非地平、尼群地平也有一定的拮抗效应,提示地西泮衍生物的抗血吸虫效应也可能与钙通道有关。
Objective To evaluate the anti-schistosomiasis effects of five diazepam derivatives B3, B7, B8, B26 and B30 and to explore their mechanism. Methods Adult male Schistosoma japonicum and adult Schistosoma mansoni were cultured in DMEM medium containing 5 kinds of diazepam derivatives B3, B7, B8, B26 and B30 respectively, and the working concentrations were 50 mol / mL , And cultured for 16 hours. The survival status of the parasites was observed under a stereomicroscope 24 hours to 72 hours after the drug was washed, and the survival rate and the rate of decrease of viability were calculated. Antagonistic effect was observed by pretreatment of the parasites with the cell line of neuron muscle relaxin D and calcium channel blocker for 1 h followed by co-culture of B3 and B30 for 16 h. Results In the experimental group B3, the survival rate and the viability of Schistosoma japonicum were 0% and 100% respectively, while the rates of Schistosoma mansoni were 20% and 93.3%. The survival rates of S. japonicum and S. mansoni were 0% And 13% respectively; the rate of vitality reduction of the two was 100% and 94.3% respectively. B7, B8, B26 experimental group anti-Schistosoma japonicum effect is not obvious, but the role of Schistosoma mansoni slightly better than Schistosoma japonicum. The inhibition of B3, B30 against Schistosoma japonicum by the antagonist B3 antagonist cells was significantly (P <0.05). The survival rate and the viability decreased by 80% and 59% ~ 63% respectively in the B3 group and 70% and 46% in the B30 group ~ 55%, the calcium channel blockers nifedipine and nitrendipine antagonistic B3, B30 after the survival rate of 10% to 40%, the viability decreased 85% to 96%. Conclusion The derivatives of diazepam B3 and B30 have significant anti-schistosome effect in vitro (P <0.01), and the sensitivity of Schistosoma japonicum to the two derivatives is better than that of Schistosoma mansoni; while the other three derivatives are resistant to Mann’s disease Schistosome effect is more obvious. Neuronoidin D had a significant antagonistic effect on B3 and B30. Nifedipine and nitrendipine had some antagonistic effects on calcium channel blockers, suggesting that the anti-schistosome effect of diazepam derivatives may also be related to calcium channel.