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细粒棘球绦虫狭义种:硫氧还蛋白过氧化物酶的沉默损害原头节向中绦期幼虫的分化。

Echinococcus granulosus sensu stricto: silencing of thioredoxin peroxidase impairs the differentiation of protoscoleces into metacestodes.

作者信息

Wang Hui, Li Jun, Zhang Chuanshan, Guo Baoping, Wei Qin, Li Liang, Yang Ning, Peter McManus Donald, Gao Xiaoli, Zhang Wenbao, Wen Hao

机构信息

Branch of The First Affiliated Hospital of Xinjiang Medical University, Changji, Xinjiang 831100, PR China - State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, PR China.

State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, PR China.

出版信息

Parasite. 2018;25:57. doi: 10.1051/parasite/2018055. Epub 2018 Nov 26.

Abstract

Cystic echinococcosis (CE) is a cosmopolitan parasitic disease caused by infection with the larval stage of Echinococcus granulosus sensu lato. Thioredoxin peroxidase (TPx) may play an essential role in the antioxidant defence system of E. granulosus s.l. as neither catalase nor glutathione peroxidase activities have been detected in the parasite. However, it is not known whether TPx affects the survival and growth of E. granulosus s.l. during development. In this study, three fragments of siRNA specific for EgTPx (siRNA-1/2/3) were designed and transfected into protoscoleces of E. granulosus sensu stricto by electroporation. Quantitative real-time PCR and Western blotting analysis showed that siRNA-3 significantly reduced the expression of EgTPx. Coincidentally, knockdown of EgTPx expression in protoscoleces with siRNA-3 significantly reduced the viability of the parasite under oxidative stress induced by 0.6 mM HO. In vitro culture studies showed that protoscoleces treated with siRNA-3 reduced pre-microcyst formation. In vivo experiments showed that injecting mice intraperitoneally with protoscoleces treated with siRNA-3 resulted in a significant reduction in the number, size and weight of CE cysts compared with those of control animals. Silencing of EgTPx led to the impairment of growth of E. granulosus s.s. both in vitro and in vivo, indicating that EgTPx is an important factor for protoscoleces survival and plays an important role in the antioxidant defence against the host during development.

摘要

囊型包虫病(CE)是一种由细粒棘球绦虫幼虫期感染引起的全球性寄生虫病。硫氧还蛋白过氧化物酶(TPx)可能在细粒棘球绦虫的抗氧化防御系统中发挥重要作用,因为在该寄生虫中未检测到过氧化氢酶和谷胱甘肽过氧化物酶活性。然而,尚不清楚TPx在发育过程中是否影响细粒棘球绦虫的存活和生长。在本研究中,设计了针对EgTPx的三个小干扰RNA片段(siRNA-1/2/3),并通过电穿孔转染到狭义细粒棘球绦虫的原头蚴中。定量实时PCR和蛋白质免疫印迹分析表明,siRNA-3显著降低了EgTPx的表达。巧合的是,用siRNA-3敲低原头蚴中EgTPx的表达,显著降低了寄生虫在0.6 mM H₂O₂诱导的氧化应激下的活力。体外培养研究表明,用siRNA-3处理的原头蚴减少了微囊前期的形成。体内实验表明,与对照动物相比,向小鼠腹腔注射用siRNA-3处理的原头蚴,导致囊型包虫囊肿的数量、大小和重量显著减少。沉默EgTPx导致狭义细粒棘球绦虫在体外和体内的生长受损,表明EgTPx是原头蚴存活的重要因素,并且在发育过程中对宿主的抗氧化防御中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e7/6254101/17fd04fb88e9/parasite-25-57-fig2.jpg

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