5种地西泮类衍生物抗血吸虫的初步评价

Preliminary evaluation on the anti-schistosoma effect of five Diazepam derivatives

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。

To investigate effects and the mechanism of the anti-schistosoma effect of five Diazepam derivatives B2、B7、B8、B26、B30（50 moL/mL） ,adult male worms of S. japonicurn and S. mansoni were suspended in DMEM and these 5 derivatives were added,then incubated for 16 hours. Worms were washed, resuspended in new and drug-free medium and observed during the following 24--72 hours under the stereomicroscope. The results showed that the survial and motility reduce rate of S. japonicum were 0% and 100% ,in contrast, S. mansoni were 20 % and 93.3 %, after exposed to B3 ,while in B30 ,the survial of S. japonicum and S. mansoni were 0% and 30% ,the motility reduce rate were 100% and 94.3% respectively. The. anti-schisto- somal effects of By ,Bs and B26 were not obvious. However, these agents were more effective on S. mansoni than that of S. japonicum. After pre-exposure for 1 hour to CyD,B3 and B30 were respectively added to the medium with schistosomes and co-incubated for 16 hours. The survial and motility reduce rate of S. japonicum were 80% and 59%--63% in B3 group,70% and 46 %- 55 % in B30 group respectively. About 10%- 40 % S. japonicum was able to survive after pre-exposure for 1 hour to nifedipine and nitrendipine and then B3 and B30 were added respectively, and the motility reduce rate was from 85% to 96%. These results showed that the activity of Diazepam derivatives B3and B30 on schistosomes was obvious in vitro. CyD could abolishes the anti-schistosomal effects of B3 and B30, while the nifedipine and nitrendipine had some effects against the anti-schistosoreal effects of B3 and B30. These findings suggest that the calcium channels of schistosome may be involved in the mechanism of the anti-schistosomat effcet of Diaiepam derivatives.