去氢骆驼蓬碱和阿苯达唑联合治疗小鼠腹腔细粒棘球蚴病的实验研究

Experimental study of harmine and albendazole on Echinococcosis infection in mice

目的观察对去氢骆驼蓬碱和阿苯达唑单用及联合用药对小鼠腹腔成熟包虫囊的作用。方法通过对昆明种小鼠腹腔注射细粒棘球蚴原头节制备包虫病动物模型并运用B超检测其成模性。将造模成功的小鼠分为模型组、去氢骆驼蓬碱组、阿苯达唑组和联合用药组及空白对照组,药物腹腔治疗14d后,检测各小鼠细粒棘球蚴湿重、抑囊率;观察小鼠肝、脑、病理组织学改变及细粒棘球蚴组织超微结构改变。结果去氢骆驼蓬碱和阿苯达唑单用及联合用药均对小鼠细粒棘球蚴有明显抑制作用,抑囊率分别为67.32%、70.50%、84.16%,差异有统计学意义(P<0.05);肝脏组织病理学观察显示,用药组均能起到改善肝脏血管周围的炎细胞浸润情况;用药组的脑组织结构均正常,无明显病理改变;囊泡染色显示,用药组囊泡的生发层结构均发生一定程度的破坏,以联合用药组较为显著;透射电镜观察囊泡超微结构,用药组的囊泡生发层细胞核破坏,核仁消失,以联合用药组较为显著。结论去氢骆驼蓬碱对小鼠棘球蚴的生长有一定的抑制作用,以联合阿苯达唑治疗效果更好,表明两种药物具有协同治疗作用。

Objective To study the effect of concomitant use of harmine and albendazole（ABZ）in mice infected with Echinococcus granulosus. Methods B ultrasound was used to examine the success rate with which an animal model of echinococcosis was created via intraperitoneal injection of E.granulosus protoscoleces（PSCs）.Mice with echinococcosis were divided into a control group,a harmine group,an ABZ group,and a combination of harmine and ABZ group.Mice in a sham group were only intraperitoneally injected with saline.After intraperitoneal injection of PSCs,mice were observed for 14 consecutive days during the drug intervention in order to evaluate the effect of drugs based on the mean cyst weight and the rate of cyst inhibition.Histopathological changes in cysts were observed with both optical and transmission electron microscopy（TEM）.Histopathological changes in the liver and brain were observed using optical microscopy. Results Results indicated that harmine alone,ABZ alone,and the combination of harmine and ABZ all markedly inhibited vesicle growth（the rate of cyst inhibition was respectively 67.32%,70.50%,and 84.16%）.Liver pathology indicated that the infiltration of inflammatory cells around the liver improved in treated groups.The structure of brain tissue in treated groups was normal,with no obvious pathological changes.The results of hematoxylin-eosin staining（HE）staining indicated that the drugs destroyed the germinal layer of vesicles.TEM results indicated the ultrastructure of vesicles was destroyed in treated groups and nucleoli disappeared.Moreover,the combination of harmine and ABZ was markedly efficacious according to HE staining and TEM results. Conclusions Results indicated that harmine was efficacious against E.granulosus,and this efficacy improved when harmine was combined with ABZ.These findings indicate that harmine and ABZ have synergistic action against echinococcosis.