人肝微粒-小鼠3T3细胞联合模型评价氟咯草酮代谢后的体外细胞毒性

发布时间：2018-05-30 11:52

本文选题：人肝微粒体-小鼠T细胞联合模型 + 氟咯草酮　；参考：《毒理学杂志》2017年05期

【摘要】：目的建立人肝微粒-小鼠3T3细胞联合模型,并应用该模型评价氟咯草酮代谢后的体外细胞毒性。方法以环磷酰胺和他莫西芬分别作为代谢增毒和代谢减毒的模型药物,建立人肝微粒体-小鼠3T3细胞联合模型。首先将环磷酰胺和他莫西芬分别配制成一系列浓度的工作溶液,加入人肝微粒体系孵育180 min后离心,将上清液与培养基1∶1混合获得孵育液。将孵育液与未经代谢的细胞供试液同时给予小鼠3T3细胞,给药48 h后,开展CCK-8试验,利用测得的吸光度(A)值,计算细胞供试液及孵育液的半数抑制浓度IC50以及IC50比值,并以IC50比值为指标评价模型药物的代谢毒性。待测化合物氟咯草酮采用与模型药物相同的方法。结果环磷酰胺IC50比值大于535.31%,经人肝微粒体代谢后对3T3细胞毒性显著增加。他莫西芬IC50比值小于5.58%,经代谢后对3T3细胞毒性显著降低。符合二者作为代谢增毒和代谢减毒代表性药物的特征。氟咯草酮IC50比值大于391.38%,表明经代谢后对3T3细胞毒性增加。结论成功建立人肝微粒-小鼠3T3细胞联合模型。待测化合物氟咯草酮经代谢后毒性增加,为进一步的毒理学研究提供参考依据。
[Abstract]:Objective to establish a joint model of human liver microparticles - mouse 3T3 cells and to evaluate the cytotoxicity of fluoxacetone in vitro. Methods cyclophosphamide and tamoxifen were used as model drugs for metabolic and metabolic detoxification, respectively, to establish a human liver microsomal mouse 3T3 cell combination model. First, cyclophosphamide and his Mo Xifen were used. The incubation solution was centrifuged after 180 min incubation with the human liver microparticle system. The incubating solution was mixed with the medium of 1: 1. The incubated liquid and the unmetabolized cells were given the test solution for the mice 3T3 cells. After the drug was given 48 h, the CCK-8 test was carried out, and the measured absorbance (A) values were used to calculate the cell test. The half inhibitory concentration of IC50 and the ratio of IC50 to the liquid and incubation fluid, and the evaluation of the metabolic toxicity of the model drug with the IC50 ratio. The results of the same method as the model drug of fluoxacetone to be measured. The results showed that the IC50 ratio of cyclophosphamide was greater than 535.31%, and the toxicity of 3T3 cells increased significantly after the metabolism of human liver microsomes. The IC50 ratio of tamoxifen. The value was less than 5.58%, and the toxicity of 3T3 cells decreased significantly after metabolism. Two were the characteristics of the metabolic and metabolic detoxification representative drugs. The IC50 ratio of flurokroacetone was greater than 391.38%, indicating that the toxicity of 3T3 cells increased after metabolism. Conclusion the combined model of human liver microparticles in mouse 3T3 cell was successfully established. The toxicities increased after the test, providing reference for further toxicological research.
【作者单位】：上海市食品药品检验所药理毒理室/药物安全评价中心;复旦大学公共卫生学院;
【基金】：国家自然科学基金(81373040)
【分类号】：R965

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