ERK抑制剂PD98059体外抗细粒棘球绦虫原头蚴作用的研究

目的探讨ERK1/2抑制剂PD98059体外抗细粒棘球绦虫原头蚴作用。方法体外培养细粒棘球绦虫原头蚴,分组后分别加入100、50、25、12.5μmol/L的PD98059后继续培养7d,利用伊红染色方法在倒置显微镜下观察原头蚴的活力,实验重复3次,绘制原头蚴活力曲线;扫描电子显微镜(SEM)下观察不同浓度PD98059组原头节表面结构改变。结果 PD98059作用1d对细粒棘球蚴原头节具有杀伤作用,第7d100μmol/L PD98059组原头节的活力仅为(12.4±0.9)%。超微结构显示原头节顶突外翻、变形,顶突界面缺损,吸盘变形,甚至出现虫蛀样损害。结论 PD98059在体外有显著的抗细粒棘球蚴原头节的作用,可认为是一种新型的抗包虫药物。

In vitro effects of the ERK inhibitor PD98059 on Echinococcus granulosus protoscoleces

Objective The aim of the present work was to determine the in vitro protoscolicidal effect of ERK inhibitor PD98059 against Echinococcus granulosus protoscoleces.Methods Protoscoleces of E.granulosus were incubated with PD98059 at concentrations of 100,50,25,and 12.5 μmol/L.Viability of protoscoleces was assessed microscopically using 0.1% eosin staining.Each experiment was repeated three times,and viability was assessed daily.Ultrastructural effects of PD98059 on E.granulosus protoscoleces in vitro were determined with SEM.Results The first signs of PD98059-induced damage were observed 1 day post-incubation.After 7 days of PD98059 incubation(100 μmol/L),the percentage of vital protoscoleces was(12.4±0.9)%.Results of vitality tests were consistent with the tissue damage observed at the ultrastructural level.The primary site of damage was the tegument of the parasite.The morphological changes included contraction of the soma region,formation of blebs on the tegument,rostellar disorganization,loss of hooks,and destruction of microtriches.Conclusion The data obtained demonstrate a clear in vitro effect of PD98059 on E.granulosus protoscoleces,and this may represent a new strategy to treat hydatid cyst echinococcosis.