摘要
目的通过观察不同浓度噻虫啉(Thia)对棘球蚴的杀伤作用,评价噻虫啉应用于治疗多房棘球蚴病的效果,旨在探索噻虫啉开发为抗包虫病先导化合物的潜能。方法体外实验中以不同浓度噻虫啉作用于多房棘球蚴原头节,以0.1%伊红染色评价原头节存活情况,并通过扫描电镜(SEM)和透射电镜(TEM)观察原头节超微结构改变。体内实验将继发性感染多房棘球蚴小鼠分为3组:模型组、阿苯达唑组(ABZ, 100 mg/kg)、Thia组(20 mg/kg),以未感染小鼠作为空白对照组。经药物灌胃治疗4 w后,分离小鼠脾脏和包虫囊肿称取重量,计算脾脏指数和抑囊率,HE染色后观察囊肿形态学改变。此外,从体外(LO2和HepG2细胞)和体内(Balb/c小鼠)评价噻虫啉毒性。结果 40μg/mL噻虫啉在体外即表现出对原头节的杀伤作用,并导致原头节体表及内部结构破坏。体内药物治疗4 w后,小鼠脾脏指数较模型组增高(P<0.05),包虫囊肿重量较模型组减轻(P<0.05)。包虫囊肿病理显示Thia组未见生发层结构。噻虫啉浓度低于80μg/mL无明显细胞毒性,20 mg/kg噻虫啉无明显的体内肝肾毒性。结论噻虫啉在体内外表现出明显的抗多房棘球蚴作用,并能增强小鼠的免疫功能,具有开发为抗包虫病先导化合物的潜能。
The aim of this study was to observe the killing effects of different concentrations of thiacloprid(Thia)on echinococcosis,and to evaluate the effects of thiacloprid in the treatment of Echinococcus multilocularis,with a view to explore the potential of thiacloprid as a lead compound against echinococcosis.In in vitro experiments,different concentrations of Thia were applied to the protoscolices of E.multilocularis.The survival of the protoscolices was evaluated with 0.1%eosin staining.The ultrastructural changes in the protoscolices were observed by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).In in vivo experiments,mice with secondary E.multilocularis infection were divided into three groups:a model group,albendazole group(ABZ,100 mg/kg)and Thia group(20 mg/kg).Mice without infection were used as the control group.After 4 weeks of intragastric administration,the spleens and hydatid cysts were isolated and weighed,the spleen index and cyst suppression rate were calculated,and the morphological changes of cysts were observed after HE staining.In addition,thiacloprid toxicity was evaluated in vitro(LO2 and HepG2 cells)and in vivo(Balb/c mice).In vitro,40μg/mL thiacloprid showed a killing effect on the protoscolices and caused the destruction of the surface and internal structure of the protoscolices.After 4 weeks of in vivo drug therapy,the spleen index of the mice was higher than that in the model group(P<0.05),and the weight of hydatid cysts was lower than that in the model group(P<0.05).The histopathology of the hydatid cysts showed no germinal layer in the Thia group.There was no significant cytotoxicity when the concentration of thiacloprid was lower than 80μg/mL,and there was no significant in vivo hepatorenal toxicity when the concentration of thiacloprid was 20 mg/kg.Thiacloprid exhibits a clear anti-E.multilocularis effect in vivo and in vitro,can enhance immune function in mice,and may have the potential to be developed as a lead compound against echinococcosis.
作者
刘川川
马兰
格日力
樊海宁
LIU Chuan-chuan;MA Lan;GE Ri-li;FAN Hai-ning(Affiliated Hospital of Qinghai University,Xining 810001,China;The Key Laboratory of Hydatidosis Research in Qinghai Province,Xining 810001,China;Research Center for High Altitude Medicine,Medical College of Qinghai University,Xining 810001,China)
出处
《中国人兽共患病学报》
CAS
CSCD
北大核心
2020年第12期1006-1013,共8页
Chinese Journal of Zoonoses
基金
国家重点研发计划项目(No.2017YFC0909900)
青海省科技厅项目(No.2019-SF-131)。
关键词
多房棘球蚴
噻虫啉
阿苯达唑
毒性
Echinococcus multilocularis
thiacloprid
albendazole
toxicity
