以ITSFn诱导法为基础的神经发育毒性评价模型的建立及其有效性研究

发布时间：2018-03-05 19:01

本文选题：胚胎干细胞　切入点：神经发育毒性　出处：《中国食品卫生杂志》2013年01期 　论文类型：期刊论文

【摘要】：目的建立体外以胰岛素-转铁蛋白-硒-纤维连接蛋白(ITSFn)培养法为基础的胚胎干细胞神经发育毒性评价模型,并对其有效性进行验证,完善神经发育毒性评价体系。方法胚胎干细胞悬滴、悬浮培养后,加入胰岛素、转铁蛋白、硒、纤维连接蛋白诱导神经细胞分化,结合细胞毒性MTT法建立神经发育毒性体外评价模型,并检测不同浓度青霉素G、苯妥英钠和氟尿嘧啶作用条件下其对胚胎干细胞神经分化能力的影响,判断受试物的神经发育毒性。结果青霉素G、苯妥英钠和氟尿嘧啶的ID50D3 nestin分别为0.017μg/ml、49.40μg/ml、1 139μg/ml,ID50D3EN-1分别0.031μg/ml、25.63μg/ml、1 762μg/ml,其发育毒性的判定均依次为无、弱和强。结论以ITSFn诱导法为基础建立的体外神经发育毒性评价模型,能够正确判定氟尿嘧啶、苯妥英钠和青霉素G的发育毒性,可用于体外神经发育毒性的筛选和评价。
[Abstract]:Objective to establish an evaluation model of neural developmental toxicity of embryonic stem cells based on insulin-transferin-selenium-fibronectin (ITSFN) culture in vitro, and to verify its effectiveness. Methods embryonic stem cells were suspended and cultured with insulin, transferrin, selenium and fibronectin to induce neuronal differentiation. Combined with cytotoxicity MTT method, a neurodevelopmental toxicity evaluation model was established in vitro, and the effects of penicillin G, phenytoin sodium and fluorouracil on the neural differentiation of embryonic stem cells under different concentrations of penicillin G, phenytoin sodium and fluorouracil were detected. Results the ID50D3 nestin of penicillin G, phenytoin sodium and fluorouracil were 0. 017 渭 g / ml, 49. 40 渭 g / ml, 1 139 渭 g / ml / ml and 1 139 渭 g / ml respectively, respectively. The developmental toxicity of penicillin G, phenytoin sodium and fluorouracil were 0. 031 渭 g / ml, 25. 63 渭 g / ml and 1 762 渭 g / ml, respectively. Conclusion the in vitro neurodevelopmental toxicity evaluation model based on ITSFn induction can correctly determine the developmental toxicity of fluorouracil phenytoin sodium and penicillin G. it can be used to screen and evaluate the in vitro neurodevelopmental toxicity of fluorouracil phenytoin sodium and penicillin G.
【作者单位】：国家食品安全风险评估中心;徐州医学院公共卫生学院;
【基金】：国家自然科学基金青年基金项目(81102134) 农业部科技行业科技项目《农药风险评估综合配套技术研究》(200903054-06)
【分类号】：R-332

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