1,9取代去氢骆驼蓬碱衍生物体外抗细粒棘球蚴作用的研究

1,9 substituted harmine derivatives against Echinococcus granulosus infection in vitro

目的研究1,9取代去氢骆驼蓬碱衍生物1-(4-甲氧基)苯基-9-丁基-β-咔啉(DH-004)、1-甲基-9-己基-β-咔啉(DH-029)和1-甲基-9-辛基-β-咔啉(DH-030)体外杀灭细粒棘球蚴的作用。方法将体外培养细粒棘球蚴分成5组:空白组、对照组和3个实验组。空白组用1%二甲基亚砜处理;对照组分别用1.56,3.12,6.25,12.50,25.00和50.00μg·mL^(-1)去氢骆驼蓬碱处理;实验1,2,3组分别用相同浓度梯度的DH-004、DH-029和DH-030处理,均干预48 h。用伊红染色法测定各组细粒棘球蚴死亡率,用透射电镜观察各组细粒棘球蚴超微结构变化。结果去氢骆驼蓬碱、DH-004、DH-029和DH-030的体外抗细粒棘球蚴作用均呈剂量依赖性。与对照组相比,实验1,2,3组均能够显著增加细粒棘球蚴死亡率,差异均有统计学意义(均P<0.01)。对照组和实验1,2,3组的半数抑制浓度分别为48.15,14.09,18.01和13.43μg·mL^(-1)。透射电镜结果显示,对照组和实验组的细粒棘球蚴细胞质出现空泡,细胞核固缩,形成层状体和脂滴,显示出显著的超微结构损伤。结论1,9取代去氢骆驼蓬碱衍生物对体外细粒棘球蚴具有明显的抑制作用。

Objective To study the 1,9 substituted harmine derivatives 1-(4-methoxy)phenyl-9-butyl-β-carboline(DH-004),1-methyl-9-hexyl-β-carboline(DH-029)and 1-methyl-9-sinki-β-carboline(DH-030)on Echinococcus granulosus in vitro.Methods The Echinococcus granulosus was divided into five groups:blank group(1%dimethyl sulfoxide);control group were treated with 1.56,3.12,6.25,12.50,25.00 and 50.00μg·mL^(-1) harmine,respectively;three experimental group were treated with the same gradient concentration of DH-004,DH-029 and DH-030,respectively.After 48 h,the eosin staining method was used to determine the mortality rate of Echinococcus granulosus,and the ultrastructural changes were observed by transmission electron microscope.Finally,the against Echinococcus granulosus activity of 1,9 substituted derivatives was evaluated in vitro.Results The control and three experimental group could inhibit the growth of Echinococcus granulosus in vitro and inhibitory effect was dose-dependent.Compared with the control group,the experimental group can significantly increase the mortality rate of Echinococcus granulosus(all P<0.01).The half-inhibitory concentration of the control and three experimental groups were 48.15,14.09,18.01 and 13.43μg·mL^(-1),respectively.Transmission electron microscope results showed that the cytoplasm of Echinococcus granulosus had vacuoles,consolidated nuclei,forming lamellar bodies and lipid droplets,which showed significant ultrastructural damage.Conclusions The 1,9 substituted harmine derivatives have a significant inhibitory effect on Echinococcus granulosus in vitro.