IGF-ⅠR抑制剂OSI-906体外抗细粒棘球绦虫原头蚴作用的研究  

In vitro effects of the IGF-ⅠR inhibitor OSI-906 on Echinococcus granulosus protoscoleces

作　　者：李娟[1,2] 赵军[2] 肖云峰[1,2] 刘辉[2] 吕国栋[2] 王建华[1,2] 

机构地区：[1]新疆医科大学基础医学院,新疆乌鲁木齐830054 [2]新疆医科大学第一附属医院

出　　处：《中国病原生物学杂志》2014年第6期534-537,共4页Journal of Pathogen Biology

基　　金：国家自然科学基金项目(No.81360251);新疆重大疾病医学重点实验室开放课题(No.SKLIB-XJMDR-2012-2);教育部长江学者和创新团队发展计划(No.IRT1181)

摘　　要：目的探讨胰岛素样生长因子I受体(insulin-like growth factor I receptor,IGF-ⅠR)抑制剂OSI-906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,用6个浓度梯度(100、50、25、12.5、6.25、3.125μmol/L)的OSI-906进行干预,分别于给药后1、2、3、4d用伊红染色,在倒置荧光显微镜下观察其活力(每组设置3个复孔),绘制原头蚴活力曲线;透射电镜下观察不同浓度OSI-906组原头节超微结构变化。结果 100和50μmol/L OSI-906作用不同时间原头蚴存活率与空白对照组组间和溶剂组相比差异有统计学意义(P<0.05);其余浓度组间比较原头蚴存活率差异无统计学意义(P>0.05)。第3d时100μmol/L的OSI-906组原头节存活率为(42.38±1.05)%;第4d时100μmol/L的OSI-906组原头蚴全部死亡。透射电镜观察OSI-906高浓度组原头蚴微毛结构消失,皮层细胞坏死,细胞膜严重破损,核形不规整,核仁大且边界不清,核基质密度极低,异染色质增多、边集。结论 IGF-ⅠR抑制剂OSI-906体外抗细粒棘球绦虫原头蚴作用显著,是一种潜在的抗包虫药物。Objective To investigate the protoscolicidai effect of insulin-like growth factor I receptor inhibitor OSI-906 on protoscoleces of Echinococcus granulosus in vitro. Methods Protoscoleces were treated with OSI-906 at a concentra- tion of 100, 50, 25, 12.5, 6.25, or 3. 125 9mol/L for 4 days, and the viability of protoscoleces was determined at 4 times （l d, 2 d, 3 d, and 4 d after treatment） using 0. 1% eosin staining. On day 4, transmission electron microscopy （TEM） was usecl to examine the ultrastructure of protoscoleces that were treated with 100μmol/L, 25 μmol/L, or 3. 125 μmol/L of OSI-906 and the control. Results OSI-906 inhibited the viability of protoscoleces, and this effect was dose- and time-dependent. Protoscoleces treated with 100 μmol/L or 50 /zmol/L of OSI-906 were significantly （P〈0.05） less viable than protoscoleces in the control group. The viability of protoscoleces treated with other concentrations of OSI-906 did not differ significantly （P〉0.05） in comparison to the control group. On day 3, the viability of protoscoleces treated with 100 μmol/L of OSI-906 was 42. 383-1.05 %, and this viability dropped to 0 % on day 4. TEM results indicated that the ultrastructure of protoscoleces treated with 100 μmol/L of OSI-906 varied dramatically on day 4. Microvilli were absent from protoscoleces, tegumental cells were necrotic, cell membranes were severely damaged, nuclei had irregular shapes, nucleoli were large but indistinct, the density of the nuclear matrix was extremely low, and there was a high level of heterochromatin and heterochromatin was marginalized. Conclusion OSI-906 inhibited the viability of the protoscoleces in vitro and may be a potential drug to treat hydatids.

关 键 词：IGF-ⅠR抑制剂 OSI-906 细粒棘球绦虫 原头蚴 体外试验 

分 类 号：R383.33[医药卫生—医学寄生虫学]