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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 effect of OSI-906, an inhibitor of insulin-like growth factor I receptor (IGF-ⅠR), against protoscoiariae of Echinococcus granulosus in vitro. Methods Echinococcus granulosus was cultured in vitro with 6 concentration gradients (100, 50, 25, 12.5, 6.25 and 3.125 μmol / L) of OSI-906, , 4d with eosin staining, observed under inverted fluorescence microscope its activity (each set of three complex holes), draw the prototrophoblast activity curve; transmission electron microscopy under different concentrations of OSI-906 group of prodromal nodules ultrastructural changes. Results The survival rates of progenitor larvae at different concentrations of 100 and 50μmol / L OSI-906 were significantly different from those of the blank control group and the solvent group (P <0.05). The survival rates of the other groups were different No statistical significance (P> 0.05). On the 3rd day, the survival rate of the primate in OSI-906 group was (42.38 ± 1.05)%. On the 4th day, all the 100-μmol / L OSI-906 group died. Transmission electron microscopy showed that the microstructure of the protoscollexin in OSI-906 disappeared, the cortical cells became necrotic, the cell membrane was severely damaged, the nuclear shape was irregular, the nucleolus was large and the boundary was unclear, the density of nuclear matrix was very low and the heterochromatin increased set. Conclusion IGF-ⅠR inhibitor OSI-906 has significant anti-Echinococcus granulosus activity against Echinococcus granulosus in vitro and is a potential anti-hydatid drug.